Analysis of the effect of in vitro dissolution on the pharmacokinetics of albendazole

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.

Evaluation of New Benzimidazole Derivatives as Cysticidal Agents: In Vitro, in Vivo and Docking Studies.

Based on our previous research on cysticidal drugs, we report the synthesis and evaluation of three new benzimidazole derivatives. In these compounds, the amido group was used as a bioisosteric replacement of the ester group. The molecular docking on ß-tubulin revealed that the derivatives interacted through hydrogen bonding with N165, E198 and V236. All compounds showed in vitro activity against Taenia crassiceps cysts. Among them, benzimidazole 3 was found to be the most potent of the series (EC50 0.86 µM). This compound also exhibited the highest probability of binding and the lowest binding free energy score and was therefore selected for in vivo evaluation. Results indicated that the efficacy of compound 3 was comparable to that of the reference drug, albendazole (50.39 vs. 47.16% parasite reduction). Animals treated with compound 3 seemed to tolerate this benzimidazole well, with no changes in behavior, or food and water consumption. These findings are consistent with the in silico prediction results, which indicated low toxicity risks. The pharmacokinetic study showed that the half-life and mean residence time (6.06 and 11.9 h, respectively) were long after oral administration. Together, these results indicate that this new benzimidazole derivative represents a promising structure with cysticidal activity.

Quinine and carbenoxolone enhance the anticonvulsant activity of some classical antiepileptic drugs.

Objective Quinine (QUIN) and carbenoxolone (CNX) elicit anticonvulsant effects typically characterized by the reduction of the epileptiform activity as well as changes in behavioral parameters related to seizures. Therefore, the aim of this study was to analyze the effects of these molecules on the anticonvulsant activity of some classical antiepileptic drugs. Methods Male Wistar rats were used. Valproate (VPA), phenytoin (PHT), or carbamazepine (CBZ) was administered at sub-therapeutic doses for intraperitoneal via. Subsequently, animals were administered with a single dose of QUIN or CNX. The anticonvulsant activity was evaluated with the maximal electroshock (MES) test and pentylenetetrazole (PTZ) administration. Additionally, the plasma levels of CBZ were determined using an HPLC method. Results All the control rats presented generalized tonic-clonic seizures after the MES test or the administration of PTZ. For the MES test, all of the antiepileptic drugs increased their anticonvulsant activity when were co-administered with QUIN. For the PTZ test, only the combination CBZ plus QUIN significantly increased the percentage of protection against the generalized tonic-clonic seizures. The co-administration of CBZ plus QUIN resulted in an augmented concentration of CBZ in plasma. Discussion The present study shows that QUIN and CNX enhance the anticonvulsant activity of some classical antiepileptic drugs. However, only the combination CBZ/QUIN had significant effects on both MES and PTZ models. Such anticonvulsant activity could be attributed to increased levels of CBZ in plasma. We propose that these molecules could improve the pharmacological actions of antiepileptic drugs administered at sub-therapeutic doses.

In vitro and in vivo cysticidal activity of extracts and isolated flavanone from the bark of Prunus serotina: A bio-guided study.

Currently, neurocysticercosis treatment involves two drugs: albendazole and praziquantel; however, their efficacy is suboptimal and new cysticidal drugs are needed. The present paper reports the cysticidal activity of extracts of the bark from Prunus serotina against Taenia crassiceps cysts and the isolation and identification of the main components of the most active extract. Results showed that all extracts displayed in vitro cysticidal activity (EC50=17.9-88.5µg/mL), being the methanolic the most active and selective. Also, methanolic extract exhibited in vivo efficacy at 300mg/kg which was similar to that obtained with albendazole. Bio-guided fractionation of methanolic extract led the isolation of 2,3-dihydro-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one (naringenin, NGN), 3,4,5-trimethoxybenzoic acid and 1,3,5-trimethoxybenzene. NGN exhibited in vitro activity, in a time-concentration-dependent manner (EC50=89.3µM]. Furthermore, NGN at a dose of 376.1µmol/kg displayed similar in vivo efficacy than those obtained with albendazole at 188.4µmol/kg. NGN also caused a high level of damage in all parasite tissue in a similar manner than that observed with the methanolic extract. This study represents the first report of the cysticidal properties of the bark of P. serotina. NGN was identified as the main active compound of this specie and other studies are required to explore the potential of this flavanone as cysticidal agent.

Essential fatty acid-rich diets protect against striatal oxidative damage induced by quinolinic acid in rats.

Essential fatty acids have an important effect on oxidative stress-related diseases. The Huntington's disease (HD) is a hereditary neurologic disorder in which oxidative stress caused by free radicals is an important damage mechanism. The HD experimental model induced by quinolinic acid (QUIN) has been widely used to evaluate therapeutic effects of antioxidant compounds. The aim of this study was to test whether the fatty acid content in olive- or fish-oil-rich diet prevents against QUIN-related oxidative damage in rats. Rats were fed during 20 days with an olive- or a fish-oil-rich diet (15% w/w). Posterior to diet period, rats were striatally microinjected with QUIN (240 nmol/µl) or saline solution. Then, we evaluated the neurological damage, oxidative status, and gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) expression. Results showed that fatty acid-rich diet, mainly by fish oil, reduced circling behavior, prevented the fall in GABA levels, increased PPARγ expression, and prevented oxidative damage in striatal tissue. In addition none of the enriched diets exerted changes neither on triglycerides or cholesterol blood levels, nor or hepatic function. This study suggests that olive- and fish-oil-rich diets exert neuroprotective effects.

Comparison of a high-performance liquid chromatography method for quantification of carbamazepine with chemiluminescent microparticle immunoassay.

Carbamazepine is an antiepileptic drug widely used for the treatment of epilepsy. In the National Institute of Neurology, monitoring has been performed using the technique chemiluminescent microparticle immunoassay (CMIA) in an automated way during the last five years. The aim of this study was to develop a simple and rapid HPLC analytical method coupled to DAD-UV detection for the determination of plasma concentrations of carbamazepine and compare its feasibility with those used in routine analysis. The developed HPLC method was fully validated and the applicability of the proposed method was verified through the analysis of plasma samples of patients and later compared with the quantification of the same plasma samples with the CMIA method. The limit of quantification obtained was 0.5 µg/mL. The mean value for recovery was 99.05% and the coefficient of variation (CV) was 5.6%. The precision and accuracy of this method were within the acceptable limits; inter- and intraday CV values were <10%. The correlation between the CMIA method and the developed HPLC method was very good (r ≈ 0.999). A Bland-Altman plot showed no significant bias between the results. The HPLC-DAD method may be an alternative to determine and monitoring the carbamazepine levels in human plasma or serum. Copyright © 2015 John Wiley & Sons, Ltd.

Gestión de cuidados con calidad desde la formación del profesional de Enfermería / Quality of care management from the training of Nursing professional

Se efectuó estudio analítico transversal con el objetivo de analizar cómo incide el proceso de formación del profesional de Enfermería en la gestión de los cuidados con calidad, en el periodo comprendido entre enero-abril 2008. El universo estuvo constituido por profesores y estudiantes, seleccionando una muestra. Las variables operacionalizadas fueron: asignaturas que enseñan a gestionar los cuidados, vínculos del sistema de conocimientos al desarrollo de habilidades profesionales, formas de organización de la enseñanza, influencia de las funciones de los profesionales de enfermería y consideraciones acerca de la calidad de los cuidados a brindar. Enseñan a gestionar cuidados con calidad técnica el 96,34 por ciento de los profesores, estableciendo el vínculo de sistemas de conocimientos con desarrollo de habilidades profesionales, gestión que se favorece con las formas de organización de la enseñanza. Las funciones asistenciales ocupan el primer lugar en la escala jerárquica, intervinieron con sus respuestas estudiantes de primer año del Nuevo Modelo Formativo, y expresan que todas las asignaturas los enseñan a gestionar cuidados con calidad mediante formas de organización de la enseñanza como conferencias, seminarios, presentación de casos y clase talleres. Profesores y estudiantes expresan desde sus ópticas cómo se percibe el proceso de gestión. El procesamiento de datos se realizó mediante el sistema SPSS. Se concluyó que el proceso de enseñanza influye de forma decisiva en la gestión de cuidados de enfermería con calidad que se brinda a los educandos(AU)

A cross-sectional and analytical study was conducted to analyze how to affect the process of training of Nursing on the quality care management from January to 'April, 2008. Universe included professors and students to select a sample. Operational variable included: subjects teaching to manage the cares, links of knowledge system to development of professional abilities, ways or teaching organization, influence of functions of nursing professionals and considerations on the quality of care to be supplied. To teach in management of care with a technical quality of the 96,34 percent of professors, establishing the link of knowledges systems with develop of professional abilities, management favored by teaching organization ways. Assistance functions are in the first place in hierarchical scale where the first year of the New Formative Form students gave their answers, expressing that all subjects teach them to manage the cars with quality be means of ways of organization of teaching as lectures, seminaries, cases presentation and workshop class. Professor and students express, from their point of view, how the management process is perceived. The data processing was carried out using the SPSS system. We conclude that the teaching process influences in a decisive way on the management of nursing care with quality offering to students(AU)

Gestión de cuidados con calidad desde la formación del profesional de Enfermería / Quality of care management from the training of Nursing professional

Se efectuó estudio analítico transversal con el objetivo de analizar cómo incide el proceso de formación del profesional de Enfermería en la gestión de los cuidados con calidad, en el periodo comprendido entre enero-abril 2008. El universo estuvo constituido por profesores y estudiantes, seleccionando una muestra. Las variables operacionalizadas fueron: asignaturas que enseñan a gestionar los cuidados, vínculos del sistema de conocimientos al desarrollo de habilidades profesionales, formas de organización de la enseñanza, influencia de las funciones de los profesionales de enfermería y consideraciones acerca de la calidad de los cuidados a brindar. Enseñan a gestionar cuidados con calidad técnica el 96,34 por ciento de los profesores, estableciendo el vínculo de sistemas de conocimientos con desarrollo de habilidades profesionales, gestión que se favorece con las formas de organización de la enseñanza. Las funciones asistenciales ocupan el primer lugar en la escala jerárquica, intervinieron con sus respuestas estudiantes de primer año del Nuevo Modelo Formativo, y expresan que todas las asignaturas los enseñan a gestionar cuidados con calidad mediante formas de organización de la enseñanza como conferencias, seminarios, presentación de casos y clase talleres. Profesores y estudiantes expresan desde sus ópticas cómo se percibe el proceso de gestión. El procesamiento de datos se realizó mediante el sistema SPSS. Se concluyó que el proceso de enseñanza influye de forma decisiva en la gestión de cuidados de enfermería con calidad que se brinda a los educandos.(AU)

A cross-sectional and analytical study was conducted to analyze how to affect the process of training of Nursing on the quality care management from January to 'April, 2008. Universe included professors and students to select a sample. Operational variable included: subjects teaching to manage the cares, links of knowledge system to development of professional abilities, ways or teaching organization, influence of functions of nursing professionals and considerations on the quality of care to be supplied. To teach in management of care with a technical quality of the 96,34 percent of professors, establishing the link of knowledges systems with develop of professional abilities, management favored by teaching organization ways. Assistance functions are in the first place in hierarchical scale where the first year of the New Formative Form students gave their answers, expressing that all subjects teach them to manage the cars with quality be means of ways of organization of teaching as lectures, seminaries, cases presentation and workshop class. Professor and students express, from their point of view, how the management process is perceived. The data processing was carried out using the SPSS system. We conclude that the teaching process influences in a decisive way on the management of nursing care with quality offering to students.(AU)

Plasma levels of clozapine and norclozapine in Mexican schizophrenia patients.

The aim of the present study was to determine the prescribing practice for clozapine (CAS 5786-21-0) as well as the plasma levels of clozapine and its main metabolite norclozapine (CAS 6104-71-8) in Mexican patients. A prospective study was performed in 69 in and out psychotic patients taking clozapine. Blood samples were taken at steady state. Plasma concentrations of clozapine and norclozapine were determined by HPLC. The results showed that the mean daily dose administered was 250 mg/d. Plasma levels showed a large interindividual variability. Mean plasma levels were 411.3 +/- 328.12 ng/mL, for clozapine and 172.0 +/- 129.9 ng/mL for norclozapine. When data were compared with those reported in other populations, it was found that although the dose was lower than that reported in Caucasians, the plasma levels were similar. As a result, the predictive models for the estimation of clozapine concentration in Caucasians were not appropriate for application in Mexican patients. The findings suggest ethnic differences in the ratio dose/plasma levels of clozapine in Mexican patients. Further studies are required to expand the observations.

In vitro characterization of some biopharmaceutical properties of praziquantel.

In several studies of patients with neurocysticercosis under treatment with praziquantel (PZQ), the pharmacokinetic data were difficult to interpret probably because of the low solubility as well as its variable oral bioavailability. Because there is limited information available regarding the biopharmaceutical properties of PZQ, the aim of this work was to evaluate the absorption characteristics of the drug and its dissolution behaviour in simulated media. Additionally, its in vitro protein binding and displacement by highly bound drugs was evaluated. Permeability evaluation was carried out by using Caco-2 cells. Dissolution release profiles were evaluated using the USP apparatus and the following dissolution media: HCl containing 2mg of sodium laurylsulfate per milliliter, milk, FeSSIF and FaSSIF. Protein binding of PZQ was carried out by equilibrium dialysis. Results showed that praziquantel was absorbed by passive diffusion. The apparent permeability constant value was 4.4x10(-5) cm/s. Binding was not influenced by the addition of highly bound drugs. Dissolution from a tablet formulation showed that the rate of praziquantel was dependent on the components of the media. Although the simulated media could explain the influence of the lipids on praziquantel absorption, they were not able to forecast the influence of carbohydrates. Further refinements are required to explain the in vivo data.

In vitro effects of albendazole sulfoxide and praziquantel against Taenia solium and Taenia crassiceps cysts.

We investigated the minimum exposure times of prazicuantel (PZQ) and albendazole sulfoxide (ABZSO) required for their activities against Taenia cysts in vitro as well as the 50 and 99% effective concentrations. The results showed that although the effects of both drugs are time and concentration dependent, ABZSO acts much slower and is less potent than PZQ.

[Comparative analysis of the influence of food and cimetidine in plasma levels of praziquantel]. / Análisis comparativo de la influencia de los alimentos y la cimetidina en los niveles plasmáticos de prazicuantel.

Praziquantel (PZQ) is an effective drug for treatment of neurocysticercosis. The drug shows an extensive first-pass effect and therefore plasma levels are low. In order to increase plasma and CSF levels of PZQ other alternatives have been investigated such as the use of PZQ jointly with cimetidine or food. With the pharmacokinetic parameters obtained in these studies, in the present work computer simulations were made in order to predict plasma concentrations of PZQ-administration with cimetidine or with meals under the two treatments currently used: ultrashort scheme (three dose of 25 mg/kg given at 2-hours intervals) and the traditional scheme (50 mg/kg/day divided in three dose given at 8-hours intervals for 15 days). The results of our simulations showed that the combination of PZQ with a high carbohydrate diet could be an adequate alternative for clinical therapy. Furthermore a clinical study was performed in 18 patients with neurocysticercosis, which received the ultrashort scheme in fasting state, with cimetidine or with a high carbohydrate diet. The efficacy of the treatment was evaluated by the percentage of disappearance of the lesions and plasma levels obtained in each group. The results showed that a high carbohydrate diet increases plasma levels of PZQ. The results of the clinical study, together with our simulations indicate that the treatment of PZQ with a high carbohydrate diet was an adequate clinical alternative and showed improvement of the effectiveness of PZQ therapy.

Interaction between grapefruit juice and praziquantel in humans.

After a single oral dose of praziquantel with 250 ml of grapefruit juice, the area under the concentration-time curve and the maximum concentration in plasma of praziquantel (Cmax) were significantly increased (Cmax for water treatment, 637.71 +/- 128.5 ng/ml; and Cmax for grapefruit juice treatment, 1,037.65 +/- 305.7 ng/ml, P < 0.05). No statistically significant differences were found in the time to maximum concentration of drug in plasma or elimination half-life.

Caracterización de los usuarios con tratamiento anticoagulante crónico del CEDIUC / Characterization of CEDIUC's users with anticoagulant chronic treatment

Durante el desarrollo de la carrera de Enfermería-obstetricia pudimos advertir que existían carencias relativas a la información disponible de grupos de pacientes sometidos a terapia con anticoagulantes orales, especificamente en lo que dice relación con caracterización biodemográfica de los integrantes del programa Tratamiento Anticoagulante Crónico (TAC). Del Centro de Diagnóstico del Hospital Clínico de la Universidad Católica de Chile (CEDIUC). Nos parece interesante clasificar la información de estos usuarios y categorizarla por grupos de edad, sexo, nivel de instrucción, patologías presentes, entre otros datos de importancia, información que permitirá programar la educación a los usuarios de acuerdo a las necesidades e interes de la población. Destaca en los resultados un promedio de edad de los usuarios de 67 años, con un predominio de población femenina (55 por ciento) y el 45 por ciento restante varones. Dentro del nivel de instrucción, destaca el 23,9 por ciento de educación básica incompleta y en el rubro ocupación el índice más alto lo muestran las dueñas de casa con 37,9 por ciento. El medicamento más utilizado es el Acenocumarol con un 95 por ciento de la población tratada. Las patologías más presentes entre los usuarios del TAC son: Fibrilación Auricular, Accidente Vascular Isquémico, Prótesis Valvular, Cardiopatía Dilatada y Valvuloplastía. Pensamos que esta información permitirá programar planes educativos que den respuesta a las necesidades reales de la población logrando, de esta manera, disminuir un número significativo de complicaciones, las que se reproducen por un inadecuado manejo del autocuidado por parte de los pacientes

Estudio epidemiológico del cólera en las comunidades de Puerto Arturo. Cunchubamba y Unamuncho / Study epidemiologist of the rage in the communities of Arturo Port. Cunchubamba and Unamuncho

Las internas rotativas de enfermería del año 1992-1993 continuando con el trabajo de investigación sobre el cólera de la comunidad de Quilian Loma realizado por la promoción de internas rotativas del año anterior hemos visto la necesidad de ampliar coberturas a otras comunidades aledañas a la mencionada como son: Cuchibamba en los barrios, El Progreso, La Dolorosa, Rocafuerte, Culapachan, San Isidro, San José, Las Carmelitas, La Merced, San Jacinto, y en Puerto Arturo, San Antonio, Unamuncho, la Primavera, Bellavista, El Conde, El Centro, el Mirador, San Francisco y la Floresta. Para realizar nuestro trabajo de investigación contamos con el tiempo de dos meses comprendido abril y mayo primero comenzamos revisando las historias clínicas de pacientes con cólera del Hospital Docente de Ambato desde febrero del 92 hasta marzo del 93, luego tabulamos los datos, finalmente pasamos al análisis mediante la elaboración de tablas con los respectivos gráficos. Trabajamos en tres subgrupos, luego de realizar un trabajo retrospectivo, una de las primeras actividades fue el recorrido de cada comunidad designada con la elaboración de croquis, delimitando los diferentes barrios existentes, los contactos con los líderes para llegar a la población con la respectiva presentación, indicamos que íbamos a realizar trabajos los fines de semana especialmente porque eran días donde se reúne la gente ya que la mayoría son agricultores, realizando también días laborales para gestiones, como solicitudes dirigidas al destacamento de Policía con el fin de conseguir señalización de tránsito, a farmacias que donan medicamentos con el objetivo de implementar botiquín a las escuelas, el trámite más importante realizado fue a la Jefatura de salud de Ambato para obtener los implementos necesarios de los puestos de U.R.O en cada unidad. Se ha puesto mucho énfasis en la educación mediante programas educativos que iban dirigidos a la población, escuelas, madres con temas como el cólera, planificación familiar, Higuiede, Alimentación todo con el fin de prevenir enfermerdades, uno de los problemas persistentes es el abastecimiento de agua ya que no es potable, demostramos a la gente como desinfectar los tanques donde almacenan el agua para mejor consumo humano. Cabe mencionar que todo lo relacionado ha sido con el apoyo de la gente, de cada comunidad, los líderes, docentes e instituciones que dieron su ayuda para alcanzar con los objetivos propuestos en este trabajo de investigación...