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1.
HSJ ; 14: 1-8, Março 2024.
Article in English | LILACS | ID: biblio-1554312

ABSTRACT

Objective: To analyze and describe the pharmacokinetic aspects of vancomycin usage in a cohort of critically ill children and to construct a pharmacokinetic model for this population. Method: We conducted an observational study in a pediatric intensive care unit from September 2017 to March 2019. Children receiving vancomycin with at least one serum measurement were included. Variables with a p-value lower than 0.2 in univariate analysis, and biologically plausible for inducing nephrotoxicity and not correlated with other predictors, were incorporated into logistic regression. Additionally, pharmacokinetic modeling was performed using the PMETRICS® package for patients with creatinine clearance (CLCR) > 30 mL/min. Result: The study included 70 children, with an average vancomycin dose of 60 mg/kg/day. Only eleven children achieved vancomycin levels within the target range (15-20 mg/L). No significant differences in doses/mg/kg/day were observed among children above, within, or below the vancomycin target range. In the multivariate model, children above the recommended serum range had an odds ratio of 4.6 [95% CI 1.4 ­ 17.2] for nephrotoxicity. A pharmacokinetic model was proposed using data from 15 children, estimating PK parameters for CLCR and V as 0.94 L/h and 5.71 L, respectively. Conclusion: Nephrotoxicity was associated with vancomycin plasma concentrations equal to or exceeding 15 mg/L. The developed model enhanced understanding of the drug's behavior within this population, potentially aiding clinical practice in dose calculations and estimation of the area under the curve ­ a recommended parameter for vancomycin monitoring.


Objetivo: Analisar e descrever os aspectos farmacocinéticos do uso de vancomicina em uma coorte de crianças sob cuidados intensivos e elaborar um modelo farmacocinético para essa população. Método: Estudo observacional em uma unidade de terapia intensiva pediátrica conduzido entre setembro de 2017 a março de 2019. Inclui-se crianças em uso de vancomicina com pelo menos uma mensuração sérica desse antimicrobiano. As variáveis com valor de p < 0,2 na análise univariada e com plausibilidade biológica para propiciar nefrotoxicidade, não correlacionadas com outras preditoras, foram incluídas na regressão logística. Adicionalmente, uma modelagem farmacocinética foi realizada usando o programa PMETRICS® para pacientes com clearance de creatinina (CLCR) > 30 mL/min. Resultado: Foram incluídas 70 crianças no estudo. A dose média de vancomicina foi de 60 mg/kg/dia. Apenas onze crianças apresentaram vancocinemia dentro da faixa alvo (15-20 mg/L). Não foram observadas diferenças significativas entre as doses administradas e a observação de vancocinemia acima, dentro ou abaixo da faixa preconizada. No modelo multivariado, crianças acima da faixa sérica preconizada apresentaram odd ratio de 4,6 [IC 95% 1,4 ­ 17,2] para nefrotoxicidade. Um modelo farmacocinético com os dados de 15 crianças foi proposto, no qual os parâmetros de PK estimados para CLCR e Volume de distribuição foram de 0,94 L/h e 5,71 L, respectivamente. Conclusão: A nefrotoxicidade mostrou-se associada às concentrações plasmáticas de vancomicina iguais ou maiores a 15 mg/L. O modelo desenvolvido permitiu entender o comportamento do fármaco nessa população e pode ser útil na prática clínica para o monitoramento do uso de vancomicina.


Subject(s)
Humans , Child , Pharmacokinetics , Multivariate Analysis
2.
Braz. J. Pharm. Sci. (Online) ; 60: e23493, 2024. tab, graf
Article in English | LILACS | ID: biblio-1533989

ABSTRACT

Abstract A novel, simple and sensitive high-performance liquid chromatography with fluorescence detection method was developed and validated for the characterization of the preclinical pharmacokinetics of melatonin under pregnant conditions. Plasma samples (25 µL) were treated with 30 µL of ethanol absolute (containing the internal standard, IS). After a centrifugation process, aliquots of supernant (5 µL) were injected into the chromatographic system. Compounds were eluted on a Xbridge C18 (150 mm x 4.6 mm i.d., 5 µm particle size) maintained at 30°C. The mobile phase consisted in a mixture of aqueous solution of 0.4% phosphoric acid and acetonitrile (70:30 v/v). The wavelengths were set at 305 nm (excitation) and 408 nm (emission) and the total analysis time was 8 min/sample. All validation tests were obtained with accuracy and precision, according to FDA guidelines, over the concentration range of 0.005-20 µg/mL. Pharmacokinetic study showed that melatonin systemic exposure increased from day 14, with a significant difference at 19 days of gestation compared to the control group. Our findings suggest a decreased metabolism of melatonin as result of temporary physiological changes that occur throughout pregnancy. However, other maternal physiological changes cannot be ruled out.


Subject(s)
Animals , Female , Rats , Plasma , Chromatography, High Pressure Liquid/methods , Melatonin/agonists , Pregnancy , Pharmacokinetics
4.
J. Health Biol. Sci. (Online) ; 11(1): 1-9, Jan. 2023. tab, ilus
Article in English | LILACS | ID: biblio-1524335

ABSTRACT

Objective: Evaluate the effectiveness of resveratrol as a hepatoprotector in a rat model of paracetamol-induced liver injury and its biodistribution to understand its pharmacokinetics. Methodology: As an experimental approach, animals were divided into the test group with 4 subgroups and the control group with 4 subgroups. Animals of the "treated" group were subjected to resveratrol pre-treatment for eight days, followed by intoxication with a high dose of paracetamol on the 8th day. Animals were euthanized to collect the blood and liver tissue samples 24 and 72 h after the last administration. Hepatoprotective activity was evaluated through serum levels of glycogen and hepatic enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), histological and morphometric analysis of the liver tissue. For biodistribution analysis, different organs (organs, kidneys, heart and lungs) were collected and macerated, and resveratrol was quantified using high-performance liquid chromatography. Statistical analyses of morphometry, transaminases and alkaline phosphatase measurements, and biodistribution results were performed using GraphPad Prism® 3.0. Differences between groups were compared using ANOVA, followed by the Bonferroni test. Statistical significance was set at p < 0.05. Results: Resveratrol has a hepatoprotective action against acute intoxication by paracetamol, as evidenced by the histological decrease in necrosis and inflammatory foci, preservation of glycogen and other 1,2-glycols in zone 3, and reduction of serum ALT and AST levels. An increased presence of collagen was observed in acinar zones 1 and 3 with picrosirius red staining; therefore, quantification was performed in these regions showing smaller collagen areas in the R and RP groups than in the PC and NC groups Paracetamol caused a significant reduction in the resveratrol concentration in serum and the organs studied, indicating that the antioxidant activity of resveratrol is related to its hepatoprotective action. Conclusion: Resveratrol has hepatoprotective properties and can mitigate some of the liver damage caused by high doses of paracetamol, as indicated by changes in tissue characteristics and liver enzyme levels.


Objetivo: Avaliar a eficácia do resveratrol como hepatoprotetor em modelo de rato com lesão hepática induzida por paracetamol e sua biodistribuição para compreender sua farmacocinética. Metodologia: Como abordagem experimental, os animais foram divididos em grupo teste com 4 subgrupos e grupo controle com 4 subgrupos. Os animais do grupo "tratado" foram submetidos ao pré-tratamento com resveratrol durante oito dias, seguido de intoxicação com alta dose de paracetamol no oitavo dia. Os animais foram eutanasiados para coleta de amostras de sangue e tecido hepático 24 e 72 horas após a última administração. A atividade hepatoprotetora foi avaliada através dos níveis séricos de glicogênio e de enzimas hepáticas, como aspartato aminotransferase (AST), alanina aminotransferase (ALT) e fosfatase alcalina (ALP), análise histológica e morfométrica do tecido hepático. Para análise de biodistribuição, diferentes órgãos (órgãos, rins, coração e pulmões) foram coletados e macerados, e o resveratrol foi quantificado por cromatografia líquida de alta eficiência. Análises estatísticas de morfometria, medidas de transaminases e fosfatase alcalina e resultados de biodistribuição foram realizadas utilizando GraphPad Prism® 3.0. As diferenças entre os grupos foram comparadas por meio de ANOVA, seguida do teste de Bonferroni. A significância estatística foi estabelecida em p < 0,05. Resultados: O resveratrol tem ação hepatoprotetora contra a intoxicação aguda por paracetamol, evidenciada pela diminuição histológica da necrose e dos focos inflamatórios, preservação do glicogênio e outros 1,2-glicóis na zona 3 e redução dos níveis séricos de ALT e AST. Foi observada presença aumentada de colágeno nas zonas acinares 1 e 3 com coloração picrosirius red; portanto, foi realizada quantificação nessas regiões mostrando menores áreas de colágeno nos grupos tratados com resveratrol e resveratrol associado com paracetamol do que nos grupos controles positivo e negativo. O paracetamol causou redução significativa na concentração de resveratrol no soro e nos órgãos estudados, indicando que a atividade antioxidante do resveratrol está relacionada à sua ação hepatoprotetora. Conclusão: O resveratrol possui propriedades hepatoprotetoras e pode mitigar alguns dos danos hepáticos causados por altas doses de paracetamol, conforme indicado por alterações nas características dos tecidos e nos níveis de enzimas hepáticas.


Subject(s)
Animals , Resveratrol , Pharmacokinetics , Hepatoprotector Drugs , Acetaminophen
5.
Braz. J. Pharm. Sci. (Online) ; 59: e22982, 2023. tab, graf
Article in English | LILACS | ID: biblio-1520311

ABSTRACT

Abstract Sepsis is described as a life-threatening organ dysfunction caused by a host's response to infection, leading to an unbalance in body homeostasis. It is one of the leading causes of death in developed countries. Considering that in critically ill patients, such as those with sepsis, plasma concentrations do not necessarily reflect tissue concentrations, one way to assess tissue concentrations is through the microdialysis technique, which allows direct measurements of free drug at the site of action. This review was carried out after searching the Pubmed, Scielo and Web of Science databases, using the following descriptors: (microdialysis AND (sepsis OR septic shock OR severe sepsis OR septicemia)) OR (microdialysis AND (sepsis OR septic shock OR severe sepsis) OR septicemia) AND (antimicrobial OR antibiotic OR antifungal)). The physiological changes generated by sepsis may imply changes in pharmacokinetic parameters, such as in clearance, which may be reduced in these patients and in volume of distribution, which presents an expansion, mainly due to edema. Both events contribute to a high inter- individual variability in tissue penetration of antimicrobials which is generally observed in patients with sepsis.


Subject(s)
Pharmaceutical Preparations/supply & distribution , Microdialysis/methods , Sepsis/pathology , Pharmacokinetics , Pharmacologic Actions , Anti-Infective Agents/pharmacology
6.
Braz. J. Pharm. Sci. (Online) ; 59: e23171, 2023. tab, graf
Article in English | LILACS | ID: biblio-1520308

ABSTRACT

Abstract Albendazole is an anthelmintic drug commonly used in parenchymal neurocysticercosis and cystic echinococcosis. The aim of this study was to explore whether disparities in the dissolution profiles of albendazole products lead to significant differences in pharmacokinetic parameters. Three generic products and the innovator were evaluated in vitro. Quality control tests were performed, and dissolution profiles were obtained according to the Mexican Pharmacopeia. Although all products passed the quality control tests, none of the generic products complied with the similarity factor (f 2). The product with the lowest f 2 value in respect to the reference was chosen for in vivo evaluation. The study was carried out in 12 healthy volunteers who received 400 mg of the generic or reference product according to a crossover design. No significant differences were found in Cmax and AUC for albendazole and its main metabolite, albendazole sulfoxide, between products. Two absorption peaks were observed in the pharmacokinetic profile, and a population (22%) with different absorption rates and delay time for the the second peak was found. Based on the results, due to the high variability in the absorption process the differences observed in vitro could not be observed in vivo.


Subject(s)
Humans , Male , Female , In Vitro Techniques/methods , Pharmacokinetics , Albendazole/analysis , Dissolution , Quality Control , Pharmaceutical Preparations/administration & dosage , Neurocysticercosis/pathology
7.
Braz. J. Pharm. Sci. (Online) ; 59: e21626, 2023. tab, graf
Article in English | LILACS | ID: biblio-1429969

ABSTRACT

Abstract n our study, we aimed to validate a method based on liquid chromatography-mass spectrometry (LC-MS) to quantify spironolactone (SPI) and its active metabolite canrenone (CAN) simultaneously in plasma samples to support in vivo experiments. Compounds were separated by using a C18 column with the isocratic elution of a mobile phase composed of 0.1% (v/v) formic acid in methanol-water (60:40 v/v) at a flow rate of 0.4 mL min−1. SPI and CAN were detected in na electrospray interface operating in a positive ionization mode and quantified using the selective ion mode monitoring of mass-charge ratios (m/z) of 439.0 for SPI and 363.1 for CAN. After calculating the matrix effect using theoretical equations, we observed the strong interference of plasma in the equipment-generated signal, which required creating analytical curves using the matrix as a solvent. The method was nevertheless linear (r 2 > 0.999) in a concentration range of 0.4-5.0 µg mL−1, as well as precise, with a coefficient of variation less than 5%. SPI's and CAN's recovery rates from the plasma ranged from 87.4% to 112.1%, while their limits of detection (i.e., 0.07 µg mL−1 and 0.03 µg mL−1, respectively) and quantification (i.e., 0.20 µg mL−1 and 0.08 µg mL−1, respectively) in the presence of plasma contaminants were low. Therefore, the bioanalytical method seems to be feasible for quantifying SPI and CAN in plasma


Subject(s)
Plasma , Mass Spectrometry/methods , Spironolactone/analysis , Canrenone/analysis , Chromatography, Liquid/methods , Pharmacokinetics , Androgen Antagonists/adverse effects
8.
Braz. J. Pharm. Sci. (Online) ; 59: e21415, 2023. tab, graf
Article in English | LILACS | ID: biblio-1439525

ABSTRACT

Abstract Dasatinib, a potent oral multi-targeted kinase inhibitor against Src and Bcr-Abl, can decrease inflammatory response in sepsis. A simple and cost-effective method for determination of an effective dose dasatinib was established. This method was validated in human plasma, with the aim of reducing the number of animals used, thus, avoiding ethical problems. Dasatinib and internal standard lopinavir were extracted from 180 uL of plasma using liquid-liquid extraction with methyl tert-butil ether, followed by liquid chromatography coupled to triple quadrupole mass spectrometry in multiple reaction monitoring mode. For the pharmacokinetic study, 1 mg/kg of dasatinib was administered to mice with and without sepsis. The method was linear over the concentration range of 1-98 ng/mL for DAS in mice and human plasma, with r2>0.99 and presented intra- and interday precision within the range of 2.3 - 6.2 and 4.3 - 7.0%, respectively. Further intra- and interday accuracy was within the range of 88.2 - 105.8 and 90.6 - 101.7%, respectively. The mice with sepsis showed AUC0-t = 2076.06 h*ng/mL and Cmax =102.73 ng/mL and mice without sepsis presented AUC0-t = 2128.46 h*ng/mL. Cmax = 164.5 ng/mL. The described analytical method was successfully employed in pharmacokinetic study of DAS in mice.


Subject(s)
Animals , Male , Mice , Plasma , Chromatography, Liquid/methods , Tandem Mass Spectrometry/methods , Dasatinib/analysis , Pharmacokinetics
9.
MedUNAB ; 25(2): 279-289, 2022/08/01.
Article in Spanish | LILACS | ID: biblio-1395815

ABSTRACT

Introducción. La Organización Mundial de la Salud (OMS) estima que más del 40% de las mujeres embarazadas a nivel mundial tienen anemia, y la mitad de estas padecen deficiencia de hierro. La prevalencia en América Latina es del 40% y en Colombia del 44.7%. Fisiológicamente en el embarazo se produce una mal llamada "anemia dilucional", existen condiciones en la embarazada que la predisponen a tener una anemia patológica. Esta última es causada principalmente por un déficit de hierro, de allí la importancia de diagnosticar a tiempo esta entidad e iniciar el manejo. La administración de hierro es la base del tratamiento de la anemia por deficiencia de hierro. Puede ser administrado por vía oral, la cual es la preferida en la mayoría de las pacientes; sin embargo, cuando este no es posible administrarlo, es esencial recurrir al hierro parenteral. No obstante, el hierro parenteral es poco usado como primera línea en el manejo de la anemia gestacional. El presente artículo tiene como objetivo realizar una revisión que permita identificar la terapia con hierro parenteral como una alternativa eficaz de manejo para la anemia gestacional, teniendo en cuenta las características farmacológicas, la administración y el uso entre las diferentes moléculas disponibles en Colombia. Metodología. Corresponde a un estudio de revisión de literatura en bases de datos y bibliotecas electrónicas, los criterios que se tuvieron en cuenta fueron textos publicados entre 1996 y 2020, en español e inglés. Se obtuvo un resultado de 95 artículos, de los cuales se seleccionaron 49. Las palabras clave para su búsqueda fueron fisiología, hierro parenteral, anemia gestacional, déficit de hierro, complicaciones del embarazo, compuestos de hierro, farmacocinética, diagnóstico y tratamiento. División de temas tratados. Fisiología; ayudas diagnósticas; características farmacológicas del hierro parenteral; ventajas, indicaciones y contraindicaciones del hierro parenteral; efectos secundarios y forma de aplicación. Conclusiones. El hierro parenteral es un tratamiento seguro y eficaz para manejar la anemia en el embarazo, se debe tener en cuenta las indicaciones y la farmacología de las moléculas para elegir la más adecuada. Además, repone más rápidamente las reservas de hierro y los niveles de hemoglobina.


Introduction. The World Health Organization (WHO) estimates that more than 40% of pregnant women worldwide have anemia, and that half of them suffer from iron deficiency. The prevalence of this in Latin America is 40%, and in Colombia, 44.7%. Physiologically, a problem called "dilutional anemia" occurs during pregnancy. There are conditions in pregnant women that predispose them to suffering from pathological anemia. The latter is mainly caused by iron deficiency, hence the importance of diagnosing this entity on time and starting treatment. Iron administration is the basis of treatment of anemia caused by iron deficiency. It can be administered orally, which is the preferred option in the majority of patients. However, when this is not possible, parenteral iron must be used. However, parenteral iron is rarely used as the first line of treatment of gestational anemia. The objective of this article is to carry out a review that allows for the identification of therapy with parenteral iron as an efficient alternative for the treatment for gestational anemia, considering the pharmacological characteristics, administration, and use among the different molecules available in Colombia. Methodology. We carried out a search in databases and electronic libraries. The criteria considered were texts published between 1996 and 2020 in Spanish and English. 95 articles were obtained, of which 49 were selected. The keywords for their search were physiology, parenteral iron, gestational anemia, iron deficit, pregnancy complications, iron compounds, pharmacokinetics, diagnosis, and treatment. Division of Covered Topics. Physiology; diagnostic aids; pharmacological characteristics of parenteral iron; advantages, indications, and contraindications of parenteral iron; secondary effects and application method. Conclusions. Parenteral iron is a safe and efficient treatment to handle anemia during pregnancy. The indications and pharmacology of the molecules must be considered to choose the most appropriate option. In addition, it replaces iron reserves and hemoglobin levels more quickly.


Introdução. A Organização Mundial de Saúde (OMS) estima que mais de 40% das mulheres grávidas em todo o mundo são anêmicas, e metade delas sofre de deficiência de ferro. A prevalência na América Latina é de 40% e na Colômbia de 44.7%. Fisiologicamente na gravidez ocorre a chamada "anemia dilucional", e existem condições na gestante que a predispõem a ter uma anemia patológica. Esta última é causada principalmente por deficiência de ferro, daí a importância de diagnosticar esta entidade a tempo e iniciar o manejo. A administração de ferro é a base do tratamento da anemia por deficiência de ferro. Pode ser administrado por via oral, o que é preferido pela maioria das pacientes; porém, quando não for possível administrá-lo dessa forma, é imprescindível recorrer ao ferro parenteral. No entanto, o ferro parenteral é raramente usado como primeira linha no manejo da anemia gestacional. O objetivo deste artigo é realizar uma revisão que permita identificar a terapia com ferro parenteral como uma alternativa eficaz de tratamento da anemia gestacional, levando em consideração as características farmacológicas, administração e uso entre as diferentes moléculas disponíveis na Colômbia. Metodologia. Foi realizada uma busca em bases de dados e bibliotecas eletrônicas, os critérios levados em consideração foram textos publicados entre 1996 e 2020, em espanhol e inglês. Foi obtido um total de 95 artigos, dos quais 49 foram selecionados. As palavras-chave para a busca foram fisiologia, ferro parenteral, anemia gestacional, deficiência de ferro, complicações na gravidez, compostos de ferro, farmacocinética, diagnóstico e tratamento. Divisão dos temas abordados. Fisiologia; auxiliares de diagnóstico; características farmacológicas do ferro parenteral; vantagens, indicações e contraindicações do ferro parenteral; efeitos colaterais e método de aplicação. Conclusões. O ferro parenteral é um tratamento seguro e eficaz para o manejo da anemia na gravidez, as indicações e farmacologia das moléculas devem ser levadas em consideração a fim de escolher a mais adequada. Além disso, reabastece mais rapidamente as reservas de ferro e os níveis de hemoglobina.


Subject(s)
Maternal Nutritional Physiological Phenomena , Anemia , Pregnancy Complications , Pharmacokinetics , Iron Compounds , Iron Deficiencies
10.
Article in Portuguese | LILACS, ECOS | ID: biblio-1411989

ABSTRACT

Objetivo: O objetivo deste trabalho foi avaliar a bioequivalência entre duas formulações de rivaroxabana 20 mg comprimido revestido, sendo a formulação teste produzida por Sanofi Medley, Brasil e a formulação referência (Xarelto®) comercializada por Bayer S/A. Métodos: Os estudos foram conduzidos em voluntários sadios de ambos os sexos e as formulações foram administradas em dose única, sob o estado de jejum e pós-prandial. Cada estudo foi conduzido de maneira independente, sendo ambos do tipo aberto, randomizado e com intervalo (washout) de sete dias entre os períodos. O estudo em jejum foi realizado em quatro períodos, com 48 voluntários, enquanto o pós-prandial foi realizado em dois períodos, com 36 voluntários. Resultados: Na administração em jejum, a razão entre a média geométrica da formulação teste e referência (T/R) de Cmáx foi de 100,77%, com intervalo de confiança de 90% (IC 90%) de 94,24% a 107,76%. Para ASC0-t, a razão T/R foi de 100,65%, com IC 90% de 96,13% a 105,39%. Na administração pós-prandial, a razão T/R de Cmáx foi de 110,63%, com IC 90% de 102,39% a 119,54%. Para ASC0-t, a razão T/R foi de 104,65%, com IC 90% de 98,44% a 109,12%. Conclusões: As formulações teste e referência foram consideradas estatisticamente bioequivalentes em ambas as condições de administração, de acordo com os critérios exigidos pela Agência Nacional de Vigilância Sanitária (Anvisa). A formulação teste foi registrada na Anvisa e disponibilizada para comercialização, contribuindo, assim, para a ampliação da disponibilidade do tratamento para doenças tromboembólicas e para a redução de custos ao paciente e ao Sistema Único de Saúde.


Objective: The objective of the present study was to evaluate the bioequivalence between two formulations of rivaroxaban 20 mg coated tablet, the test formulation being manufactured by Sanofi Medley, Brazil and the reference formulation (Xarelto® ) commercialized by Bayer S/A. Methods: The studies were conducted in healthy volunteers of both sexes and the formulations were administered in a single dose, under fasting and fed conditions. Each study was conducted independently, both being open-label, randomized and with a seven-day interval (washout) between periods. The fasting study was carried out in four periods, with 48 volunteers, while the fed study was carried out in two periods, with 36 volunteers. Results: In the fasting administration, the ratio between.


Subject(s)
Thromboembolism , Pharmacokinetics , Therapeutic Equivalency
11.
Vitae (Medellín) ; 29(1): 1-8, 2022-01-09. Ilustraciones
Article in English | LILACS, COLNAL | ID: biblio-1363721

ABSTRACT

Background: In developing countries, particularly in Iraq, the use of generic medicines has been increasing in recent years, primarily as a cost-saving measure in healthcare provision. In the Iraqi market, famotidine tablets are available from different pharmaceutical companies. As a result, regular pre-marketing quality testing is required to check the quality and identify which product might safely substitute the innovator product in the event of the innovator brand's unavailability or high cost. Objective: various quality control tests have been conducted to determine the Pharmaceutical Equivalence of the different generic and brands of Famotidine film-coated tablets marketed in Iraq. Materials and Methods: Four different samples of the most commonly available Famotidine 20 mg tablets in the Iraqi market were tested for drug contents, friability, and hardness. Additionally, the in-vitro drug release and kinetics were evaluated. Results: slight differences in the products' content were found; however, they were within the acceptable requirement of British Pharmacopeia (BP) and The United States Pharmacopoeia (USP) 30, NF 25. Similarly, the friability and hardness were within the excellent range according to the B.P. and USP. The results of our study indicated that the tested brand (Famodin) and the three generic products (Famosam, Ulceran, and Famodar) of Famotidine tablets have a unique pattern of in-vitro release profiles. However, all the tested brands and generic pills complied with the USP specifications for the immediate release dosage forms except for Famosam. Release kinetic for the four tested products indicates first-order kinetic models. Conclusion: The findings revealed that nearly all of the tested Famotidine tablet brands and generics met the pharmacopeial requirements for oral tablets. As a result, if acquiring the innovative brand of famotidine tablets is difficult to obtain, healthcare providers may be advised to use the tested products instead


Antecedentes: En los países en vías de desarrollo, especialmente en Irak, el uso de medicamentos genéricos ha aumentado en los últimos años, principalmente como medida de ahorro en la prestación de servicios sanitarios. En el mercado iraquí, los comprimidos de famotidina están disponibles en diferentes empresas farmacéuticas. Por ello, es necesario realizar periódicamente pruebas de calidad previas a la comercialización para comprobar la calidad e identificar qué producto podría sustituir con seguridad al producto innovador en caso de que éste no esté disponible o tenga un coste elevado. Objetivo: se han realizado varias pruebas de control de calidad para determinar la Equivalencia Farmacéutica de los diferentes genéricos y marcas de Famotidina comprimidos recubiertos con película comercializados en Irak. Materiales y métodos: Se analizaron cuatro muestras diferentes de los comprimidos de 20 mg de Famotidina más comunes en el mercado iraquí para determinar el contenido de fármaco, la friabilidad y la dureza. Además, se evaluó la liberación in-vitro del fármaco y su cinética. Resultados: Se encontraron ligeras diferencias en el contenido de los productos; sin embargo, estaban dentro de los requisitos aceptables de B.P. y de la Farmacopea de Estados Unidos (USP) 30, NF 25. Así mismo, la friabilidad y la dureza estaban dentro del rango excelente según la B.P. y la USP. Los resultados de nuestro estudio indicaron que la marca probada (Famodin) y los tres productos genéricos (Famosam, Ulceran y Famodar) de comprimidos de famotidina tienen un patrón único de perfiles de liberación in-vitro. Sin embargo, todas las marcas y los comprimidos genéricos probados cumplieron con las especificaciones de la USP para las formas farmacéuticas de liberación inmediata, excepto Famosam. La cinética de liberación de los cuatro productos probados indica modelos cinéticos de primer orden. Conclusiones: Los resultados revelaron que casi todas las marcas y genéricos de comprimidos de Famotidina probados cumplían los requisitos farmacopeicos para los comprimidos orales. En consecuencia, si resulta difícil adquirir la marca innovadora de comprimidos de famotidina, se puede aconsejar a los profesionales sanitarios que utilicen los productos probados en su lugar


Subject(s)
Humans , Pharmaceutical Preparations , Pharmacokinetics , Drugs, Generic
12.
Braz. J. Pharm. Sci. (Online) ; 58: e19321, 2022. tab, graf
Article in English | LILACS | ID: biblio-1420424

ABSTRACT

Abstract To investigate the pharmacokinetics and pharmacodynamics of Astragali Radix-Corni Fructus herb-pair in kidney-yin deficiency model, which was made by continuously oral gavage of thyroxine. A simple and rapid LC-MS/MS method was developed and validated for the determination of loganin and morroniside in rat plasma and used for the pharmacokinetics study. The kidney-yin deficiency significantly changed the AUC(0-∞), Cmax and CLz/F of loganin and morroniside. The T1/2z of morroniside increased significantly in the kidney-yin deficiency rats. For the pharmacodynamics study, the liver index, kidney index, and ALT, TBIL, UREA, CREA level in the kidney-yin deficiency mice were examined. The herb-pair had been proved to be effective for the treatment of kidney-yin deficiency by affecting the liver, kidney, ALT, UREA and CREA, which showed positively correlated with the dose. The pharmacokinetics and pharmacodynamics studies in the pathological status could offer more valuable information for the future application of Astragali Radix-Corni Fructus herb-pair.


Subject(s)
Animals , Male , Rats , Pharmacokinetics , Yin Deficiency/classification , Pharmacologic Actions , Kidney/abnormalities , Plants, Medicinal/adverse effects , Plant Extracts/analysis , Astragalus propinquus/adverse effects , Liquid Chromatography-Mass Spectrometry/methods
13.
Braz. J. Pharm. Sci. (Online) ; 58: e201875, 2022. tab, graf
Article in English | LILACS | ID: biblio-1403725

ABSTRACT

Abstract Two polyurethane foam-based sorbents (PUF) were synthesized by imprinting and grafting techniques and examined for selective separation and preconcentration of caffeine (CAF) in some pharmaceutical products and in black tea. Molecularly imprinted PUF was synthesized based on hydrogen-bonding interactions between CAF and alizarin yellow G (AYG) and subsequent polymerization into PUF. The static experiments indicated optimum sorption conditions at pH=6.5 and 5.5 for imprinted PUF (AY-IPUF) and grafted PUF (AY-GPUF), respectively. In the online experiments, the suitable preconcentration time was found to be 40 and 20s for (AY-IPUF) and (AY-GPUF), respectively, at a flow rate of 1.75 mL.min-1. Desorption of CAF has been affected by passing 500 µL of 0.05, 0.01 mol.L−1 HCl eluent onto (AY-IPUF) and (AY-GPUF), respectively. The online methods have provided satisfactory enrichment factors of 8.4 and 10.5 for (AY-IPUF) and (AY-GPUF), respectively. The time consumed for preconcentartion, elution and determination steps was 1.48 and 1.05 min, thus, the throughput was 42 and 57 h-1, for (AY-IPUF) and (AY-GPUF), respectively. The developed sorbents were studied for the determination of CAF in pharmaceutical samples which will be helpful to minimize caffeinism. Finally, in silico bioactivity, ADMET and drug-likeness predictive computational studies of caffeine were also carried out


Subject(s)
Polyurethanes/adverse effects , Caffeine/adverse effects , Polymerization , Tea , Pharmacokinetics , Pharmaceutical Preparations/analysis , Hydrogen-Ion Concentration
14.
Braz. J. Pharm. Sci. (Online) ; 58: e18881, 2022. tab, graf
Article in English | LILACS | ID: biblio-1420489

ABSTRACT

Abstract Tuberculosis treatment consists of a drug combination, where isoniazid is the core drug and alcoholism is a factor highly related to poor patient compliance with the therapy. CYP2E1 is an enzyme involved both in the metabolism of ethanol and in the formation of hepatotoxic compounds during the metabolism of isoniazid. The shared metabolism pathway accounts for the possibility of pharmacokinetic interaction in cases of concomitant alcohol use during tuberculosis treatment. The aim of this study was to evaluate the effect of repeated exposure of Wistar rats (males, 250 g, n=6) to ethanol on the pharmacokinetics of a single dose of isoniazid in combination with pyrazinamide and rifampicin (100 mg/kg, 350 mg/kg and 100 mg/kg, respectively). An animal group received the combination of drugs and ethanol and was compared to a control group, which received the combination of drugs without exposure to ethanol. The plasma concentrations of isoniazid were determined by a UHPLC/UV bioanalytical method that was previously validated. Biochemical markers of liver function were measured to assess potential damage. A lower elimination half-life of isoniazid was observed in the ethanol group than in the control group (t1/2 0.91 h versus 1.34 h). There was no evidence of hepatotoxicity through the biomarker enzymes evaluated. The results allow us to infer that although there are no biochemical changes related to liver damage, there is a slight influence of ethanol exposure on the pharmacokinetic profile of isoniazid. This change may have a relevant impact on the efficacy of isoniazid in the outcome of tuberculosis treatment.


Subject(s)
Animals , Male , Rats , Pharmacokinetics , Ethanol/adverse effects , Isoniazid/analysis , Tuberculosis/pathology , Biomarkers/analysis , Cytochrome P-450 CYP2E1/pharmacology
15.
São Paulo; s.n; s.n; 2022. 63 p. tab, tab.
Thesis in Portuguese | LILACS | ID: biblio-1396298

ABSTRACT

Introdução: Meropenem (MER) e Piperacilina/Tazobactana (PTZ) são agentes antimicrobianos largamente prescritos para pacientes grandes queimados internados em Unidade de Terapia Intensiva (UTI) com infecções nosocomiais causadas por Gram-negativos sensíveis CIM 2 mg/L, Enterobacteriaceae, EB e Non-enterobacteriaceae, NEB. A síndrome da resposta inflamatória sistêmica (SRIS) que ocorre durante o choque séptico no grande queimado pode causar alteração na farmacocinética do paciente em terapia intensiva, de modo que a dose recomendada pode não atingir o alvo desejado contra Gram-negativos de sensibilidade intermediária CIM >2 mg/L. Objetivo: Investigar a efetividade dos beta-lactâmicos piperacilina e meropenem na infusão estendida comparada à infusão intermitente recomendada, para os pacientes sépticos grandes queimados através da abordagem farmacocinética-farmacodinâmica (PK/PD). Ética, casuística e procedimentos: Autor e co-autores declararam não haver conflito de interesse. O protocolo foi aprovado, registro CAAE 07525118.3.0000.0068. No presente protocolo de estudo investigaram-se 36 pacientes sépticos grandes queimados, ambos os gêneros (12F/24M) em terapia intensiva do choque séptico com piperacilina-tazobactana 4,5g q6h ou meropenem 1g q8h. Os pacientes incluídos foram estratificados em dois grupos com base na administração através da infusão intermitente, 0,5 h (G1) ou da infusão estendida, 3 h (G2), ambos com 16 pacientes cada. Duas amostras sanguíneas (1,5mL/cada) foram coletadas no estado de equilíbrio (Steady State), 3ª e 5ª hora do início da infusão. Os níveis séricos de PTZ e MER foram mensurados através de cromatografia líquida, e a farmacocinética (PK) dos dois grupos de pacientes foi comparada aos dados reportados em voluntários sadios. A abordagem PK/PD foi aplicada para avaliação da cobertura do antimicrobiano a partir da estimativa do índice de predição de efetividade (% fΔT>CIM) e da probabilidade de alcançar o alvo terapêutico (PTA) com base no alvo PK/PD recomendado, 100%fΔT>CIM. Resultados e discussão: As características de admissão dos pacientes G1/G2 foram expressas através de mediana e interquartil: Clcr 115 (90-148) / 127 (90-170) ml/min; 30 (24-31) / 27 (24- 33,5) anos, 70 (61-75) / 71 (65-75) kg, 30 (20-42) / 33,9 (18-38,4)% área total de superfície queimada, SAPS3 53 (45-57) / 48 (37,8-59,5). Na admissão dos pacientes na UTI registrou-se G1/G2: trauma térmico (17/16), trauma elétrico (1/2), lesão inalatória (11/11), ventilação mecânica (16/9) e vasopressores foram necessários em 15/8 pacientes, G1/G2. Ocorreram diferentes alterações na farmacocinética dos dois beta-lactâmicos após a infusão estendida versus a infusão intermitente quando comparadas com dados relatados em voluntários sadios. Evidenciou-se prolongamento da meia vida decorrente do aumento do volume de distribuição. Estes resultados impactaram diferentemente a cobertura. O monitoramento de biomarcadores inflamatórios expressos em medianas (G1/G2) evidenciou aumento do PCR: 232/183mg/L e leucocitose (leucócitos 11/14 mil cel/mm3, neutrófilos 9/10 mil cel/mm3) na fase precoce do choque séptico. Relativamente à microbiologia dos isolados, a erradicação dos patógenos ocorreu para todos os pacientes após a infusão estendida contra Gram-negativos sensíveis (CIM: 2 mg/L), e de sensibilidade intermediária (CIM 4mg/L) como a K. pneumoniae e P. aeruginosa, enquanto a infusão intermitente garantiu erradicação de patógenos apenas até CIM 2 mg/L. Conclusão: Evidenciou-se a superioridade da infusão estendida frente à infusão intermitente na cobertura dos dois antimicrobianos, no alvo terapêutico considerado 100%fΔT>CIM. Registraram-se alterações na farmacocinética destes agentes nos pacientes frente aos dados reportados para voluntários sadios. Diferença significativa entre grupos (G1/G2) foi encontrada com relação meia vida biológica, e ao volume de distribuição tanto pata a piperacilina quanto para o meropenem


Background: Meropenem (MER) and Piperacillin/Tazobactam (PTZ), antimicrobial betalactam agents are widely prescribed to burn patients from the Intensive Care Unit (ICU) with nosocomial infections caused by Gram-negative strains. Change in the pharmacokinetics of critically ill patient occurs during the systemic inflammatory response syndrome (SIRS) at the course of septic shock. Then, the recommended dose administered by intermittent infusion, 0.5 hr cannot reach the target against gram-negative strains MIC > 2 mg/L. Subject: To investigate drug effectiveness of the beta-lactams piperacilin and meropenem in extended infusion compared to the recommended intermittent infusion in critically ill septic burn patients using pharmacokinetic-pharmacodynamic (PK/PD) approach. Ethics, Casuistry and Methods: All authors declared there is no conflict of interests. Ethical approval CAAE, register 07525118.3.0000.0068. It was investigated in the study protocol 36 septic burn patients of both genders (12M / 24F), undergoing antimicrobial therapy with PTZ 4.5 g q6h or MER 1g q8h. Based on the chosen antimicrobial therapy and drug infusion prescribed by the physician, patients were stratified in groups with intermittent 0.5h infusion (G1) or with the extended 3h infusion (G2), both groups with 16 patients each. Two blood samples were collected at the steady state (1.5mL / each), at the 3rd and 5th hrs of starting the infusion. Serum levels were measured by liquid chromatography. Pharmacokinetics (PK) of MER or PTZ was compared to data reported in healthy volunteers for both groups of patients. PK/PD approach was applied to estimate the drug effectiveness index (fΔT> MIC) and to assess the probability of target attained (PTA) based on the recommended PK/PD target, 100% fΔT> MIC. Results and discussion: Characteristics of patients admission G1/G2 were: Clcr 115(90- 148)/127(90-170) ml/min; 30(24-31)/27(24-34) yrs, 70(61-75)/71(65-75) kg, 30(20- 42)/33.9(18-38.4)% total burn surface area, SAPS3 53(45-57)/48(37.8-59.5), medians (interquartile): thermal trauma occurred (17/16), electric trauma (1/2), inhalation injury (11/11), mechanical ventilation (9/16) and vasopressors required in 15/8 patients. It was demonstrated that different PK changes occurred for both beta-lactam agents after the extended or intermittent infusion by comparison with data reported in healthy volunteers. PK changes were related to the prolongation of biological half-life and increases on volume of distribution with impact on pharmacodynamics. On the other hand, meropenem total body clearance reduced by 50% at the earlier period of septic shock could be explained by the reduction of MER-transporters expression in the tubular renal secretion, once only patients with renal function preserved were included in the study protocol. Inflammatory biomarkers increased at the earlier period of septic shock: C-rp 232/183mg/L; leukocytes 11/14*103cel/mm3, neutrophils 9/10*103cel/mm3, medians, G1/G2. Clinical and microbiological cure was obtained for all patients of G1 against MIC < 2mg/L after intermittent 0.5 h infusion; while PK/PD target was attained for G2 patients undergoing antimicrobial therapy with MER or PTZ by extended infusion against gram negative strains K. pneumoniae, P. aeruginosa up to MIC 4mg L. Conclusion: Superiority of the extended infusion over intermitent infusion was obtained for the two antimicrobials was evidenced, in the therapeutic target considered 100%fΔT>CIM. Changes in the pharmacokinetics of these agents were recorded in patients compared to data reported for healthy volunteers. A significant difference between groups (G1/G2) was found in relation to biological half-life and volume of distribution for both piperacillin and meropenem


Subject(s)
Piperacillin/analysis , Burns/diagnosis , Meropenem/analysis , Patients/classification , Shock, Septic/complications , Pharmacokinetics , Pharmaceutical Preparations , Cross Infection/complications , Chromatography, Liquid/methods , Critical Illness/classification , Systemic Inflammatory Response Syndrome/diagnosis , Pharmacologic Actions , Enterobacteriaceae , Dosage , Intensive Care Units/classification , Anti-Infective Agents/analysis
16.
Rev. cuba. endocrinol ; 32(2): e277, 2021. tab, graf
Article in Spanish | LILACS, CUMED | ID: biblio-1347402

ABSTRACT

Introducción: La aplicación de actividades fijas en el tratamiento del hipertiroidismo con I131 (yoduro de sodio, conocido también como radioyodo), es el método más usado en nuestro país, a pesar de la individualidad morfo-funcional que caracteriza esta afección. Sin embargo, no existe aún, un consenso internacional sobre la dosis más conveniente para cada caso, y por ende, los resultados no siempre son los deseados. Objetivo: Evaluar la aplicabilidad de varios métodos de cálculo de dosis paciente-específica para el tratamiento de hipertiroidismo con yoduro de sodio. Métodos: Se realizó un análisis de los resultados de varios métodos de cálculo de dosis recomendados internacionalmente a partir de la actividad fija prescrita en 10 pacientes, con el empleo de tecnologías y herramientas ya desarrolladas y disponibles en el país. Se evaluó la variabilidad inter-especialista y su impacto en la dosis planificada para el tratamiento. Resultados: El uso de la información incompleta de la biodistribución y farmacocinética del paciente produjo diferencias entre -42 por ciento y 37 por ciento de las dosis para el mismo paciente. El resultado de la comparación del método de cálculo recomendado por la Sociedad Europea de Medicina Nuclear, manejando la masa por gammagrafía-2D / 3D y por ultrasonido, arrojó diferencias no significativas entre sí. La variabilidad inter-especialista de las actividades prescrita mostró diferencias significativas, que arrojan sobre el mismo paciente, discrepancias entre 44Gy y 243Gy de las dosis terapéuticas a recibir, situación que puede comprometer el éxito del tratamiento y producir efectos secundarios no deseados. Conclusiones: Las técnicas dosimétricas paciente-específicas se pueden implementar satisfactoriamente en nuestro país. Las diferencias numéricas encontradas, especialmente la variabilidad inter-especialista, demuestran la no estandarización terapéutica, lo que apoya el uso de la farmacocinética paciente-específica pre terapéutica y la masa por gammagrafía-3D para planificar el tratamiento siempre que sean posible(AU)


Introduction: Despite of its typical morpho-functional individuality, fixed activities remain as the most used method in Cuba for hyperthyroidism treatment with I (sodium iodide, also known as radioiodine). However, there is not yet an international consensus on the most convenient doses for each case, so, the results are not always the desired ones. Objective: To evaluate the applicability of various patient-specific dose calculation methods for the treatment of hyperthyroidism with sodium iodide. Methods: It was carried out an analysis in 10 patients of the results of some methods for dose calculation from the prescribed fixed activity recommended internationally, with the use of technologies and tools already developed and available in the country. The inter-specialist variability and its impact in the planned dose for the treatment were assessed. Results: The use of uncompleted biodistribution and pharmacokinetics information of the patient showed differences between -42 percent and 37 percent in the doses for the same patient. The outcome of the comparison of the calculation method recommended by the European Society of Nuclear Medicine managing the mass by 3D/2D gammagraphy and ultrasound, presented no significant discrepancies among them. The inter-specialist variability of prescribed activity was statistically significant, and it can produce in the same patient differences between 44Gy and 243Gy of the therapeutic doses, which could affect the treatment success and lead to unnecessary side effects. Conclusions: The patient´s personalized calculation methods can be satisfactorily applied in Cuba. The numeric differences found, especially inter-specialist variability, show the lack of therapeutic standardization, which supports the use of pre-therapeutic patient-specific pharmacokinetics and the mass by 3D-gammagraphy to plan the treatment when possible(AU)


Subject(s)
Humans , Male , Female , Adult , Sodium Iodide/therapeutic use , Pharmacokinetics , Hypothyroidism/therapy , Nuclear Medicine/methods , Reference Standards
17.
Revista Digital de Postgrado ; 10(2): 312, ago. 2021. ilus, tab
Article in Spanish | LILACS, LIVECS | ID: biblio-1418905

ABSTRACT

El mecanismo específico por el cual los esteroides actuarían sobre la inflamación pulmonar sostenida, así como la definición del mejor fármaco a utilizar e incluso la duración adecuada del tratamiento, siguen siendo objetivo de estudio de los ensayos clínicos en curso. Como médicos clínicos, creemos que las potentes propiedades antiinflamatorias de los esteroides sintéticos están bien definidas, y aún falta evidencia definitiva de que otras estrategias antiinflamatorias proporcionen una mejor eficacia, al menos en el COVID-19. Aunque los esteroides sintéticos comparten una marcada acción antiinflamatoria y escasos efectos mineralocorticoides, su bioequivalencia y diferentes cinéticas deben considerarse cuidadosamente, debido a la elevada variabilidad de la farmacocinética individual, uso y prescripción adecuada de estos fármacos, ya que pueden desencadenar efectos adversos diversos que podrían impactar negativamente el curso clínico del paciente con COVID-19. Además, muchos de los fármacos actualmente considerados en el manejo del paciente con esta patología pueden potenciar la vida media y la aparición de efectos adversos de los corticoesteroides, o algunos efectos adversos de estos otros fármacos pueden simular complicaciones asociadas al uso de corticoesteroides, lo que podría conllevar a una suspensión precoz e inoportuna de los mismos. Números estudios clínicos y artículos basados en revisiones narrativas han servido de guías para los médicos clínicos en medio de esta pandemia, sin embargo, sus resultados deben interpretarse con cautela. Por estas razones, hemos realizado un análisis con base en el sistema GRADE de estos estudios para contrastar la información incluida en los estudios clínicos y minimizar el error de análisis(AU)


e specific mechanism by which steroids would act on sustained lung inflammation, as well as the definition of the best drug to use and the appropriate treatment duration remain to be the objectives of ongoing clinical trials. As clinicians, we believe that the potent anti-inflammatory properties of synthetic steroids are well defined and definitive evidence that other anti-inflammatory strategies provide better efficacy is still lacking, at least in COVID-19. Although synthetic steroids share a pronounced anti-inflammatory action and few mineralocorticoid effects, their bioequivalence and different kinetics should be considered, due to the high variability of individual pharmacokinetics, the appropriate use and prescription of these drugs, given that they could trigger various effects that could negatively impact the clinical course of the patient with COVID-19. In addition, many of the drugs currently considered in the management of the patient with this disease can enhance the half-life and appearance of adverse effects of corticosteroids and some adverse effects of these other drugs can simulate complications associated with the use of corticosteroids, which could lead to an early and untimely suspension of them. Numerous clinical studies and study articles based on narrative reviews have served as guides for clinicians in the midst of this pandemic; however, the results of these should be interpreted with caution. For these reasons, we have performed an analysis based on the GRADE system of these studies to contrast the information included in the clinical studies and minimize the error of analysis(AU)


Subject(s)
Steroids , Adrenal Cortex Hormones , Pandemics , COVID-19 , Mineralocorticoids , Pneumonia , Pharmacokinetics , Pharmaceutical Preparations , Health Strategies , Duration of Therapy , Anti-Inflammatory Agents
18.
Vitae (Medellín) ; 28(3): 1-14, 2021-08-11. Ilustraciones
Article in English | LILACS, COLNAL | ID: biblio-1363261

ABSTRACT

Background: Milk-derived biopeptides have reported in vitro dipeptidyl-peptidase IV (DPP-IV) inhibition, suggesting a glycemic-regulatory effect in Type 2 Diabetes Mellitus (T2DM). Nonetheless, the therapeutic application of these nutraceuticals is limited by the scarcity of knowledge regarding their pharmacokinetic profile. Objective: This study aimed to characterize and assess the pharmacokinetics of milk-derived biopeptides. Through an in silico comparative analysis with gliptins, we expected to identify enhanced properties in food-hydrolysates and suitable DPP-IV inhibiting peptides as candidates for T2DM therapy. Methods: A comparison between gliptins and biopeptides was conducted based on in silico evaluation of drug-likeness, physicochemical properties, pharmacokinetics, and synthetic accessibility. Suitable target proteins for gastrointestinal-absorbable biopeptides were determined as well. Data collection was performed on SwissADME, ADMETlab, DrugBank, SwissTargetPrediction, ChemDes, and BIOPEP-UWM platforms. Statistical analysis was carried out using a one-way ANOVA test. Results: Drug-likeness compliance showed no significant difference between gliptins and biopeptides (p>0.05) in three out of nine assessed rules, though gastrointestinal-absorbable biopeptides exhibited no significant difference with gliptins in five drug-likeness guidelines. The physicochemical evaluation revealed a significant difference (p<0.05) between both groups, with peptides exhibiting enhanced solubility, flexibility, and polarity. Nine out of thirty-six assessed biopeptides reported being likely gastrointestinal-absorbable molecules, from which six displayed ≥30% predicted bioavailability, two reported CYP450 interactions, and all were determined to be blood confined. Biopeptides showed a slightly lower clearance than gliptins yet counteracted by a significantly lower half-life. Moreover, synthetic accessibility scores indicated higher synthetic ease for biopeptides. In addition, absorbable bioactive peptides reported a considerable binding affinity to DPP-IV and Calpain-I. Conclusions: Compared to gliptins, gastrointestinal-absorbable biopeptides exhibit superior physicochemical properties (higher solubility, flexibility, and polarity), lesser CYP450 interactions, higher synthetic ease, and some reported an important affinity for DPP-IV and Calpain-I. Only a small fraction of milk-derived biopeptides are suitable drug-like compounds and feasible candidates for T2DM therapy; yet, testing their therapeutic potency remains subject to further studies


Antecedentes: Los biopéptidos derivados de la leche han mostrado inhibir la dipeptidil-peptidasa IV (DPP-IV) en ensayos in vitro, lo que sugiere una regulación de la glicemia en la Diabetes Mellitus Tipo 2 (DM2). Sin embargo, su uso terapéutico está limitado por el escaso conocimiento de sus propiedades farmacológicas. Objetivo: Caracterizar y evaluar el perfil farmacocinético de los biopéptidos derivados de la leche. Por medio de un análisis comparativo in silico, se buscó identificar propiedades de carácter superior a las gliptinas en los biopéptidos inhibidores de DPP-IV, así como posibles candidatos a agentes terapéuticos en la DMT2. Métodos: Se llevó a cabo una comparación entre las Gliptinas y los biopéptidos basada en la evaluación in silicode las características "d r ug - li ke", propiedades fisicoquímicas, farmacocinética y accesibilidad sintética. Adicionalmente, se determinaron posibles proteínas diana para los biopéptidos de alta probabilidad de absorción gastrointestinal. Los datos se obtuvieron en SwissADME, ADMETlab, DrugBank, SwissTargetPrediction, ChemDes y BIOPEP-UWM. El análisis estadístico se basó en un análisis de varianza (one-way ANOVA test). Resultados: El cumplimiento de las reglas de "drug-likeness" no mostró diferencias significativas entre las gliptinas y los biopéptidos (p>0.05) en tres de las nueve normas evaluadas, empero, los biopéptidos absorbibles no mostraron diferencias significativas con las gliptinas en cinco de estas. La evaluación fisicoquímica reveló una diferencia significativa (p>0.05) entre ambos grupos y una mayor solubilidad, flexibilidad y polaridad para los biopéptidos. Nueve de los treinta y seis biopéptidos estudiados reportaron alta probabilidad de absorción gastrointestinal, de los cuales seis presentaron una biodisponibilidad predicha ≥30%, dos reportaron interacciones con el CYP450, y todos mostraron permanecer confinados en sangre. Los biopéptidos mostraron una tasa de aclaramiento inferior a las gliptinas, sin embargo, contrarrestado por una vida-media significativamente menor. Los valores de accesibilidad sintética indicaron una mayor facilidad de síntesis para los biopéptidos. Por último, los biopéptidos absorbibles mostraron una considerable afinidad por la DPP-IV y la Calpaína-I. Conclusiones: Frente a las gliptinas, los biopéptidos absorbibles presentan: propiedades fisicoquímicas superiores (mayor solubilidad, flexibilidad y polaridad), menores interacciones con el CYP450, mayor facilidad de síntesis y algunos una importante afinidad por la DPP-IV y la Calpaína-I. Una mínima fracción de biopéptidos derivados de la leche son candidatos viables para la terapia de DM2; sin embargo, la determinación de su efectividad terapéutica permanece sujeta a futuros estudios


Subject(s)
Humans , Pharmacokinetics , Peptides , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors
19.
Rev. bras. ciênc. vet ; 28(2): 75-80, abr./jun. 2021. il.
Article in Portuguese | LILACS, VETINDEX | ID: biblio-1367182

ABSTRACT

O objetivo deste trabalho foi avaliar a eficácia do florfenicol na dose usualmente empregada em equinos de 22 mg/kg pelas vias intravenosa, intramuscular e oral para o tratamento de adenite equina por Streptococcus equi. subsp. equi, usando a modelagem farmacocinética/farmacodinâmica (PK/PD ­ Pharmacokinetic/Pharmacodynamic) e a simulação de Monte Carlo. Foi realizada uma simulação de Monte Carlo a partir dos parâmetros PK, logo depois, efetuou-se a modelagem PK/PD para determinar as taxas de eficácia do antimicrobiano para o tratamento dessa infecção bacteriana, de acordo com o valor da concentração inibitória mínima (CIM), em um intervalo de CIM de 0,125 ­ 4 µg/mL. Pela via intravenosa, a probabilidade de erradicação bacteriana foi de 100% para CIM até 0,5 µg/mL e efeito bacteriostático com probabilidades de 99% e 80% para CIMs de 2 e 4 µg/mL, respectivamente. Já pelas vias intramuscular e oral a probabilidade de se atingir o índice de erradicação bacteriológica foi de 100% para CIM de até 0,5 µg/mL, contudo, atinge valores de 80% e 81%, respectivamente, para CIM de 1 µg/mL considerando o efeito bactericida (p<0,01). Portanto, através desse estudo é evidenciado a eficácia do florfenicol até a CIM de 0,5 µg/mL para as três vias de administração citadas, entretanto, para CIMs superiores a esse valor, é imprescindível o ajuste da dose farmacológica, evitando falhas na terapêutica e possível resistência microbiana.


The objective of this study was to evaluate the efficacy of florfenicol at the dose usually used in horses of 22 mg/kg by intravenous, intramuscular and oral routes for the treatment of equine adenitis caused by Streptococcus equi. subsp. equi, using Pharmacokinetic/Pharmacodynamic (PK/PD) modeling and Monte Carlo simulation. A Monte Carlo simulation was performed from the PK parameters, then PK/PD modeling was performed to determine the antimicrobial efficacy rates for the treatment of this bacterial infection, according to the minimum inhibitory concentration (MIC) value, in a MIC range of 0.125 - 4 µg/mL. Intravenously, the probability of bacterial eradication was 100% for MICs up to 0.5 µg/mL, and the bacteriostatic effect was 99% and 80% for MICs of 2 and 4 µg/mL, respectively. However, for the intramuscular and oral routes, the probability of reaching the bacteriologic eradication index was 100% for MICs of up to 0.5 µg/mL, however, it reaches values of 80% and 81%, respectively, for MICs of 1 µg/mL considering the bactericidal effect (p<0.01). Therefore, through this study the efficacy of florfenicol is evidenced up to the MIC of 0.5 µg/mL for the three routes of administration cited, however, for MICs higher than this value, it is essential to adjust the pharmacological dose, avoiding failures in therapy and possible microbial resistance.


Subject(s)
Animals , Horse Diseases/therapy , Lymphadenitis/veterinary , Anti-Bacterial Agents/therapeutic use , Pharmacokinetics , Monte Carlo Method
20.
Rev. bras. ciênc. vet ; 28(2): 75-80, abr./jun. 2021. graf, tab
Article in Portuguese | LILACS, VETINDEX | ID: biblio-1491705

ABSTRACT

O objetivo deste trabalho foi avaliar a eficácia do florfenicol na dose usualmente empregada em equinos de 22 mg/kg pelas vias intravenosa, intramuscular e oral para o tratamento de adenite equina por Streptococcus equi. subsp. equi, usando a modelagem farmacocinética/farmacodinâmica (PK/PD – Pharmacokinetic/Pharmacodynamic) e a simulação de Monte Carlo. Foi realizada uma simulação de Monte Carlo a partir dos parâmetros PK, logo depois, efetuou-se a modelagem PK/PD para determinar as taxas de eficácia do antimicrobiano para o tratamento dessa infecção bacteriana, de acordo com o valor da concentração inibitória mínima (CIM), em um intervalo de CIM de 0,125 – 4 μg/mL. Pela via intravenosa, a probabilidade de erradicação bacteriana foi de 100% para CIM até 0,5 μg/mL e efeito bacteriostático com probabilidades de 99% e 80% para CIMs de 2 e 4 μg/mL, respectivamente. Já pelas vias intramuscular e oral a probabilidade de se atingir o índice de erradicação bacteriológica foi de 100% para CIM de até 0,5 μg/mL, contudo, atinge valores de 80% e 81%, respectivamente, para CIM de 1 μg/mL considerando o efeito bactericida (p<0,01). Portanto, através desse estudo é evidenciado a eficácia do florfenicol até a CIM de 0,5 μg/mL para as três vias de administração citadas, entretanto, para CIMs superiores a esse valor, é imprescindível o ajuste da dose farmacológica, evitando falhas na terapêutica e possível resistência microbiana.


The objective of this study was to evaluate the efficacy of florfenicol at the dose usually used in horses of 22 mg/kg by intravenous, intramuscular and oral routes for the treatment of equine adenitis caused by Streptococcus equi. subsp. equi, using Pharmacokinetic/Pharmacodynamic (PK/PD) modeling and Monte Carlo simulation. A Monte Carlo simulation was performed from the PK parameters, then PK/PD modeling was performed to determine the antimicrobial efficacy rates for the treatment of this bacterial infection, according to the minimum inhibitory concentration (MIC) value, in a MIC range of 0.125 - 4 μg/mL. Intravenously, the probability of bacterial eradication was 100% for MICs up to 0.5 μg/mL, and the bacteriostatic effect was 99% and 80% for MICs of 2 and 4 μg/mL, respectively. However, for the intramuscular and oral routes, the probability of reaching the bacteriologic eradication index was 100% for MICs of up to 0.5 μg/mL, however, it reaches values of 80% and 81%, respectively, for MICs of 1 μg/mL considering the bactericidal effect (p<0.01). Therefore, through this study the efficacy of florfenicol is evidenced up to the MIC of 0.5 μg/mL for the three routes of administration cited, however, for MICs higher than this value, it is essential to adjust the pharmacological dose, avoiding failures in therapy and possible microbial resistance.


Subject(s)
Animals , Horses/physiology , Horses/injuries , Pharmacokinetics , Lymphadenitis/therapy , Lymphadenitis/veterinary , Thiamphenicol/analogs & derivatives , Thiamphenicol/pharmacokinetics , Thiamphenicol/pharmacology , Streptococcus equi
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