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1.
Mem. Inst. Invest. Cienc. Salud (Impr.) ; 18(3)dic. 2020. ilus, ilus
Article in Spanish | LILACS, BDNPAR | ID: biblio-1337583

ABSTRACT

El Alprazolam pertenece a las benzodiazepinas. Sus efectos se atribuyen a que actúa sobre receptores de membrana específicos, lo cual facilita la acción inhibitoria presináptica y postsináptica del ácido γ-aminobutírico (GABA), especialmente en la formación reticular ascendente. Se utiliza para el tratamiento de los estados de ansiedad, crisis de angustia, ataques de pánico y estrés intenso. Este estudio se realizó para analizar los parámetros comparativos de control de calidad in vitro mediante la evaluación de la variación de peso, friabilidad, dureza, tiempo de desintegración, perfil y eficiencia de disolución entre el medicamento innovador (Xanax®) y multifuentes que son comercializados en el mercado peruano. Para realizarlo, se seleccionaron tabletas de Alprazolam 0,5 mg multifuente de diferentes laboratorios comparándolos con el medicamento innovador y se evaluaron las características fisicoquímicas y biofarmacéuticas. Los ensayos farmacopeicos se evaluaron según lo establecido en la USP 42. Los resultados de las pruebas fisicoquímicas indicaron que las muestras analizadas no tenían diferencia significativa y estaban dentro de lo establecido en la farmacopea, así mismo el perfil y eficiencia de disolución permitieron establecer que el comportamiento biofarmacéutico de las mismas era muy similar para ambos tipos de molécula. Se estableció que las tabletas multifuentes de Alprazolam 0,5 mg de esta investigación son bioequivalentes con el innovador, por lo que permite proponer a la comunidad científica la determinación de la equivalencia biofarmacéutica como elemento de apoyo en la toma de decisiones de compra en el servicio farmacéutico


Alprazolam belongs to benzodiazepines. Its effects are attributed to the fact that it acts on specific membrane receptors, which facilitates the presynaptic and postsynaptic inhibitory action of γ-aminobutyric acid (GABA), especially in the ascending reticular formation. It is used to treat anxiety states, panic attacks, and intense stress. This study was carried out to analyze comparative parameters of in vitro quality control by evaluating the variation in weight, friability, hardness, disintegration time, profile and dissolution efficiency between the innovative drug (Xanax®) and multi-sources tablets that are marketed in the Peruvian market. To perform this, Alprazolam 0.5 mg multi-source tablets were selected from different laboratories comparing them with the innovative medicine and the physicochemical and biopharmaceutical characteristics were evaluated. Pharmacopoeial trials were evaluated as established in USP 42. The results of physicochemical tests indicated that analyzed samples did not have a significant difference and were within the established in the pharmacopoeia, as well as the profile and dissolution efficiency allowed to establish that their biopharmaceutical behavior was very similar for both types of molecules. It was established that Alprazolam 0.5 mg multi-source tablets from this research are bioequivalent with innovator, which makes it possible to propose to scientific community determination of biopharmaceutical equivalency as a support element in decision-making process for purchasing services pharmacist


Subject(s)
Alprazolam/administration & dosage , Alprazolam/therapeutic use , Interchange of Drugs , Quality Control , Therapeutic Equivalency
2.
Rev. colomb. cardiol ; 27(4): 262-269, jul.-ago. 2020. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1289224

ABSTRACT

Resumen Objetivo: Evaluar la equivalencia terapéutica de dos marcas comerciales de bisoprolol -hidroclorotiazida como terapia antihipertensiva. Método: Estudio prospectivo, doble ciego, doble falso, aleatorizado, de grupos paralelos, en el que se evaluó el efecto antihipertensivo de la combinación de bisoprolol-hidroclorotiazida 2,5-6,25 y 5-6,25 mg (comprimidos BHL, formulación test) y bisoprolol-hidroclorotiazida 2,5-6,25 y 5-6,25 mg tabletas (BHM, formulación de referencia), administrados en pacientes con hipertensión arterial. Variables de efectividad: Presiones arteriales medidas mediante mediante esfigmomanómetro de mercurio al inicio y después del período placebo, a las 4 y 8 semanas del inicio del tratamiento; cambios horarios de la presión arterial durante 24 horas, mediante monitorización ambulatoria de la presión arterial. Resultados: El control de los valores de presión arterial se logró en ambas formulaciones, principalmente a partir de la cuarta semana de tratamiento. Los pacientes del grupo test ingresaron con presiones arteriales sistólicas más elevadas. Después del tratamiento no hubo diferencias entre los grupos, a ninguno de los tiempos. La relación V/P del grupo test fue 0,5-1. Los índices de suavidad de ambos fueron mayores a 1,75. Conclusiones: La formulación test de la combinación de bisoprolol-hidroclotiazida demostró acción antihipertensiva similar al compararla con la formulación de referencia.


Abstract Objective: To evaluate the therapeutic equivalence of two commercial brands of bisoprolol -hydrochlorothiazide as antihypertensive therapy. Method: A prospective, double blind, double placebo, randomised, parallel group study was conducted, in which the antihypertensive effect of the bisoprolol -hydrochlorothiazide 2.5 - 6.25 mg and 5 - 6.25 mg (tablets BHL, test formula) and bisoprolol -hydrochlorothiazide 2.5 - 6.25 mg and 5 - 6.25 mg tablets (BHM, reference formula), was compared by administering it to patients with arterial hypertension given to patients with arterial hypertension. Effectivity variables: blood pressures measured using a mercury sphygmomanometer at the beginning and after the placebo period, at 4 weeks and 8 weeks from the start of the treatment; blood pressure hours change during 24 hours using an ambulatory blood pressure monitoring device. Results: Control of the blood pressure values was achieved with both formulas, mainly from the fourth week of treatment. The patients of the test group were admitted with higher systolic blood pressures. After the treatment, there were no differences between the groups at any of the times. The V/P ratio of the test group was 0.5 - 1. The smoothness index in both groups was greater than 1.75 of fit of both was greater than 1.75. Conclusions: The test formula of the bisoprolol-hydrochlorothiazide demonstrated an antihypertensive action similar to that achieved with the reference formula.


Subject(s)
Humans , Male , Female , Adult , Therapeutic Equivalency , Bisoprolol , Hydrochlorothiazide , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Hypertension
3.
Medwave ; 20(1): e7825, 2020.
Article in English, Spanish | LILACS | ID: biblio-1087898

ABSTRACT

Los medicamentos constituyen un bien económico que forma parte del gasto público y privado y de la toma de decisiones en salud. El aseguramiento de su calidad, eficacia y seguridad resulta fundamental. Sin embargo, la variada oferta disponible en el mercado chileno, donde se reconocen productos innovadores y genéricos, constituye un escenario confuso para consumidores y proveedores en salud. En esta revisión pretendemos aclarar los conceptos de fármacos bioequivalentes (aplicable a compuestos de tamaño molecular pequeño) y fármacos biosimilares (para compuestos biológicos de mayor complejidad molecular). En ambos casos, el comportamiento en el organismo del principio activo debe ser demostrado mediante estudios realizados para este fin. Una aplicación directa del concepto de bioequivalencia es la intercambiabilidad, definida como la posibilidad de utilizar un producto de un mismo principio activo, mientras la forma farmacéutica y esquema de dosificación sean iguales. Las normas relativas a esta materia y los organismos públicos encargados, no solo debieran garantizar la seguridad y la eficacia en el intercambio entre productos, sino también aspectos relacionados con el costo, la accesibilidad a los fármacos y la implementación de una guía de homogeneización de conceptos y criterios de intercambiabilidad basados en la evidencia, lo cual impactaría en una mejor educación para los usuarios, reduciendo la asimetría de información entre el usuario y la industria. La importancia de la intercambiabilidad destaca en Chile en el contexto del Plan de Garantías Explícitas en Salud (GES) y la Ley de Protección Financiera para Diagnósticos y Tratamientos de Alto Costo en Salud (Ley Ricarte Soto). Sin embargo, no es posible garantizar que todos los productos alternativos al innovador presentes en el mercado chileno son bioequivalentes. El conocimiento disponible en esta temática puede impactar y contribuir a la toma de decisiones en los prescriptores y usuarios, así como en la elaboración de políticas públicas en torno a los productos farmacéuticos bioequivalentes y biosimilares en nuestro país.


Medicines are an economic good and a fundamental component of public and private health spending and decision-making. Assurance of their quality, efficiency, and safety is essential. In Chile, the wide variety of available drugs, including innovator products, and generics­some of which are certified as bioequivalent, while others are not­creates a potentially confusing scenario for both consumers and health providers. In this review, we intend to shed light on the concepts of bioequivalency (the standard permitting interchangeability for small-molecule drugs) and biosimilarity (the standard permitting interchangeability for biological compounds of greater molecular complexity). In both cases, how the active substance interacts with the host organism must be demonstrated by studies designed and carried out for this purpose. Interchangeability is defined as the possibility of using a product of the same active principle, as long as the pharmaceutical form and dosage scheme are the same. Regulations related to bioequivalence and biosimilarity must not only guarantee safety and efficacy when products are interchanged but also facilitate cost savings and access to medicines. Implementation of evidence-based guidelines that standardize concepts of interchangeability could lead to more educated usage and reduced information asymmetry between patients (users) and industry. Drug interchangeability is particularly relevant in two government health initiatives in Chile: the Explicit Guarantees in Health Care (GES) plan, and the Law on Financial Protection for High-Cost Diagnostics and Treatment in Health Care (also known as the "Ricarte Soto Law"). Nonetheless, it is not possible to guarantee that all alternative drug products on the Chilean market are bioequivalents of the reference product. Synthesis of the available knowledge on bioequivalent and biosimilar pharmaceutical products in Chile could facilitate and contribute to stakeholder decision-making and the development of better health policies.


Subject(s)
Therapeutic Equivalency , Drugs, Generic , Biosimilar Pharmaceuticals , Chile , Legislation, Drug
4.
Article in English | WPRIM | ID: wpr-773365

ABSTRACT

OBJECTIVE@#To develop methods for determining a suitable sample size for bioequivalence assessment of generic topical ophthalmic drugs using crossover design with serial sampling schemes.@*METHODS@#The power functions of the Fieller-type confidence interval and the asymptotic confidence interval in crossover designs with serial-sampling data are here derived. Simulation studies were conducted to evaluate the derived power functions.@*RESULTS@#Simulation studies show that two power functions can provide precise power estimates when normality assumptions are satisfied and yield conservative estimates of power in cases when data are log-normally distributed. The intra-correlation showed a positive correlation with the power of the bioequivalence test. When the expected ratio of the AUCs was less than or equal to 1, the power of the Fieller-type confidence interval was larger than the asymptotic confidence interval. If the expected ratio of the AUCs was larger than 1, the asymptotic confidence interval had greater power. Sample size can be calculated through numerical iteration with the derived power functions.@*CONCLUSION@#The Fieller-type power function and the asymptotic power function can be used to determine sample sizes of crossover trials for bioequivalence assessment of topical ophthalmic drugs.


Subject(s)
Administration, Topical , Clinical Trials as Topic , Methods , Cross-Over Studies , Humans , Models, Theoretical , Ophthalmic Solutions , Pharmacokinetics , Sample Size , Therapeutic Equivalency
5.
Article in English | WPRIM | ID: wpr-761930

ABSTRACT

Proton-pump inhibitors (PPIs) are effectively used to treat acid-related diseases, including gastroesophageal reflux disease (GERD); however, many unmet medical needs still exist. As a new treatment option, potassium-competitive acid blockers (P-CABs), such as tegoprazan, have been developed. This study was performed to compare the pharmacokinetics (PKs) between two formulations (test and reference drugs) of tegoprazan 100 mg tablets. A randomized, single oral dose, two-treatment, two-period, two-sequence study was conducted with 12 healthy subjects. Each subject received the test drug or reference drug in the first period and the alternative treatment in the second period. For PK evaluation, blood samples were collected up to 48 hours post-dose in each period. The plasma concentrations of tegoprazan and its active metabolite (M1) were measured by liquid chromatography-tandem mass spectrometry. PK parameters, including maximum plasma concentration (C(max)) and area under the concentration-time curve from zero to the last measurable time (AUC(last)), were estimated using a non-compartmental method. The plasma concentration-time profiles of the two formulations were comparable. The geometric mean ratios [90% confidence intervals (CIs)] of the test drug to the reference drug for C(max) and AUC(last) were 0.98 (0.85–1.12) and 1.03 (0.93–1.13), respectively. The corresponding values of M1 were 0.99 (0.89–1.11) and 1.01 (0.93–1.09), respectively. The two formulations of tegoprazan exhibited comparable PK profiles, fulfilling the regulatory criteria for bioequivalence.


Subject(s)
Gastroesophageal Reflux , Healthy Volunteers , Humans , Male , Mass Spectrometry , Methods , Pharmacokinetics , Plasma , Tablets , Therapeutic Equivalency
6.
Article in English | WPRIM | ID: wpr-786681

ABSTRACT

Combination therapies of antihypertensive drugs are recommended in cases where hypertension is not controlled by monotherapy. This study aimed to compare the pharmacokinetics (PKs) between fixed-dose combination (FDC) of fimasartan/amlodipine 60/10 mg and the corresponding loose combination. Because of the high intra-subject variability for maximum plasma concentration (C(max)) of fimasartan, a randomized, open-label, 3×3 partial replicated crossover design was adopted. Subjects received a single dose of FDC of fimasartan/amlodipine 60/10 mg or the corresponding loose combination in each period. Blood samples for PK analysis were collected up to 48 hours for fimasartan and 144 hours for amlodipine, respectively. Geometric mean ratios (GMRs) and its 90% confidence intervals (CIs) of the FDC to the loose combination for C(max) and area under the concentration-time curve from time 0 to the last quantifiable time point (AUC(last)) were calculated. Sixty healthy subjects were randomized, and 57 subjects completed the study. The concentration-time profiles of fimasartan and amlodipine were similar between the FDC and loose combination. The GMRs (90% CIs) of the FDC to the loose combination for C(max) and AUC(last) were 1.0440 (0.9202–1.1844) and 1.0412 (0.9775–1.1090) for fimasartan, and 1.0430 (1.0156–1.0711) and 1.0339 (1.0055–1.0631) for amlodipine, respectively. The GMRs and its 90% CIs for C(max) and AUC(last) of fimasartan and amlodipine were included not only in the scaled bioequivalence criteria but also in the conventional bioequivalence criteria. In conclusion, FDC of fimasartan/amlodipine 60/10 mg showed comparable PK profiles with the corresponding loose combination, which suggests their bioequivalence.


Subject(s)
Amlodipine , Antihypertensive Agents , Cross-Over Studies , Healthy Volunteers , Hypertension , Pharmacokinetics , Plasma , Therapeutic Equivalency
7.
Cad. Saúde Pública (Online) ; 35(10): e00053519, 2019. graf
Article in Portuguese | LILACS | ID: biblio-1039383

ABSTRACT

Resumo: Produtos biológicos revolucionaram a terapêutica mundial. O alto custo desses medicamentos, no entanto, ameaça a sustentabilidade dos sistemas de saúde. O desenvolvimento de cópias é tido como uma alternativa econômica, mas devido à complexidade desses produtos, muitos conceitos utilizados para os medicamentos genéricos não se aplicam. A intercambialidade entre produtos biológicos representa um desafio regulatório a ser superado. Este ensaio discute os principais desafios regulatórios relacionados ao estabelecimento de critérios para intercambialidade entre produtos biológicos novos e suas cópias no âmbito do Sistema Único de Saúde (SUS), considerando as diretrizes adotadas pelas principais agências reguladoras de medicamentos do mundo sobre a intercambialidade e o arcabouço regulatório vigente no Brasil para esta questão. Preocupações relacionadas à intercambialidade de produtos biológicos incluem substituição automática, nomenclatura, farmacovigilância, imunogenicidade e extrapolação das indicações terapêuticas e dos dados clínicos de produtos biológicos novos para suas cópias. Embora o sucesso clínico e os benefícios econômicos da alternância entre alguns produtos biológicos novos e seus biossimilares já tenham sido observados, a heterogeneidade das barreiras regulatórias para aprovação das cópias de produtos biológicos entre diferentes países deve ser considerada para a regulamentação da intercambialidade de produtos biológicos no Brasil.


Abstract: Biological products have sparked a worldwide therapeutic revolution. However, the high cost of these products threatens health systems' sustainability. The development of copies is considered an economic alternative, but due to the products' complexity, many concepts used in generic drugs do not apply. Interchangeability between biologicals poses a regulatory challenge. This essay discusses the main regulatory challenges for establishing criteria for interchangeability between new biologicals and their copies in the scope of the Brazilian Unified National Health System (SUS), considering the guidelines adopted by the world's main drug regulatory agencies concerning interchangeability and the prevailing Brazilian regulatory framework on this issue. Concerns related to the interchangeability of biologicals include automatic substitution, nomenclature, pharmacovigilance, immunogenicity, and extrapolation of therapeutic indications and clinical data from new biologicals to their copies. While the clinical success and economic benefits of switching from new biologicals to their biosimilars have already been observed, the heterogeneity between countries in the regulatory barriers to the approval of copies of biologicals should be taken into consideration during the regulation of interchangeability of biologicals in Brazil.


Resumen: Los productos biológicos revolucionaron la terapéutica mundial. El alto coste de estos medicamentos, no obstante, amenaza la sostenibilidad de los sistemas de salud. El desarrollo de copias se considera como una alternativa económica, pero debido a la complejidad de estos productos, muchos conceptos utilizados para los medicamentos genéricos no se aplican a los mismos. La intercambiabilidad entre productos biológicos representa un desafío regulatorio que se debe superar. Este trabajo discute los principales desafíos regulatorios, relacionados con el establecimiento de criterios para la intercambiabilidad entre productos biológicos nuevos y sus copias en el ámbito del Sistema Único de Salud (SUS), considerando las directrices adoptadas por las principales agencias regulatorias de medicamentos del mundo sobre la intercambiabilidad y el armazón regulatorio vigente en Brasil para esta cuestión. Las preocupaciones relacionadas con la intercambiabilidad de productos biológicos incluyen la sustitución automática, nomenclatura, farmacovigilancia, inmunogenicidad y extrapolación de las indicaciones terapéuticas, así como de los datos clínicos de productos biológicos nuevos para sus copias. A pesar de que el éxito clínico y los beneficios económicos de la alternancia entre algunos productos biológicos nuevos y sus biosimilares, ya se han observados, la heterogeneidad de las barreras regulatorias para la aprobación de las copias de productos biológicos entre los diferentes países debe ser considerada para la regulación de la intercambiabilidad de productos biológicos en Brasil.


Subject(s)
Humans , Biological Products , Biosimilar Pharmaceuticals , Legislation, Drug , Brazil , Therapeutic Equivalency , Drugs, Generic , Drug Approval , Pharmacovigilance , Legislation, Pharmacy , National Health Programs
8.
S. Afr. fam. pract. (2004, Online) ; 62(2): 40-44, 2019. tab
Article in English | AIM, AIM | ID: biblio-1270131

ABSTRACT

Purpose: In everyday practice clinicians are overwhelmed by claims from the pharmaceutical industry and, due to marketing efforts, they often view generic multisource products with scepticism despite proof and registration by regulatory authorities of bioequivalence. The primary aim of this study was exploratory and aimed to compare the acceptability of generic cefpodoxime (Cepodem®) versus the innovator brand product (Orelox®) in terms of effectiveness, safety and tolerability in a general private setting in South Africa in the treatment of upper and lower respiratory tract infections.Methods and patients: Ninety patients were recruited and randomised to receive either product for 10 days after clinical diagnoses of either tonsillo-pharyngitis or rhino-sinusitis or pneumonia.Results: It was demonstrated that both products resulted in similar clinical and bacteriological cure rates with also no difference in tolerability profiles. Conclusion: These findings support the bioequivalence data as submitted for regulatory approval, of the generic Cepodem® translating into clinical effectiveness and argues against the need for a clinical non-inferiority study to demonstrate sameness


Subject(s)
Cephalosporins , Therapeutic Equivalency
9.
Neumol. pediátr. (En línea) ; 13(2): 75-80, mar. 2018. tab, graf
Article in Spanish | LILACS | ID: biblio-947306

ABSTRACT

Introduction. The early use of systemic steroids has been associated with a decrease in the rate of hospitalizations in pediatric patients with asthma exacerbation. The objective was to compare the equivalence of two forms of administration, as well as to determine the optimal time for its indication. Material and methods: Observational, randomized, open study of equivalence, comparing oral versus parenteral steroids. The primary outcomes were changes in the severity scale and the rate of hospitalizations. The secondary result was the time until improvement was reached. ANOVA and Chi square tests were used to determine the statistical significance; it was considered significant when p <0,05. Results: In both groups both the severity scale and the hospitalization rate were considerably modified with early administration. At 30 minutes after using hydrocortisone (p<0,05). The greatest variation in the severity scale was observed. Conclusion: both routes of administration proved to be effective and should be used early.


Introducción: El uso precoz de los esteroides sistémicos ha sido asociado con disminución de la tasa de hospitalizaciones en los pacientes pediátricos con exacerbación asmática. El objetivo de este estudio es comparar la equivalencia de dos formas de administración, así como determinar el tiempo óptimo para su indicación. Material y métodos: Estudio observacional, aleatorizado, abierto de equivalencia, comparando esteroides por via oral contra parenteral. Los outcomes primarios fueron los cambios en la escala de gravedad y la tasa de hospitalizaciones y el secundario fue el tiempo en alcanzar la mejoría. Se utilizó ANOVA, prueba Chi cuadrado para determinar las significaciones estadísticas, se consideró significancia p<0,05. Resultados: En ambos grupos tanto la escala de gravedad como la tasa de mortalidad se modificaron de forma importante con la administración precoz. A los 30 minutos de administrar hidrocortisona (p<0,05) se observó la mayor variación en la escala de gravedad. Conclusión: ambas vías de administración demostraron ser efectivas y deben ser usadas de forma precoz.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Asthma/drug therapy , Adrenal Cortex Hormones/administration & dosage , Anti-Asthmatic Agents/administration & dosage , Recurrence , Asthma/physiopathology , Time Factors , Therapeutic Equivalency , Chi-Square Distribution , Administration, Oral , Analysis of Variance , Observational Study
10.
Article in English | WPRIM | ID: wpr-742403

ABSTRACT

Solifenacin is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms. Solifenacin tartrate is a newly developed salt formulation of solifenacin. This study compared the pharmacokinetic and safety properties after single-dose administration of solifenacin tartrate (test formulation) and solifenacin succinate (reference formulation) in healthy male volunteers. A total of 36 subjects were enrolled in this randomized, open-label, single-dose, two-way crossover study. During each treatment period, subjects received the test formulation or reference formulation. Plasma samples were collected at pre-dose and at 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48 and 72 hours post-dose. Safety was assessed by adverse events, physical examinations, laboratory assessments, 12-lead electrocardiograms, and vital signs. Thirty-three subjects completed the study and were included in the pharmacokinetic analysis. The mean (standard deviation) values of AUC(last) for the test and reference formulations were 486.98 (138.47) and 469.07 (128.29) h·ng/mL, respectively. The mean (standard deviation) values of C(max) for the test and reference formulations were 14.66 (3.85) and 14.10 (3.37) ng/mL, respectively. The 90% confidence intervals for AUC(last) and C(max) were 0.9702 to 1.1097 and 0.9779 to 1.0993, respectively. All adverse events were mild or moderate, and there were no serious adverse events. The pharmacokinetic properties of solifenacin tartrate were similar to those of solifenacin succinate and met the acceptance criteria for bioequivalence. Both formulations were safe, and no significant difference was observed in the safety assessments of the formulations.


Subject(s)
Cross-Over Studies , Electrocardiography , Humans , Male , Pharmacokinetics , Physical Examination , Plasma , Solifenacin Succinate , Therapeutic Equivalency , Urinary Bladder, Overactive , Vital Signs , Volunteers
11.
Article in English | WPRIM | ID: wpr-742397

ABSTRACT

Because bioequivalence studies are performed using a crossover design, information on the intra-subject coefficient of variation (intra-CV) for pharmacokinetic measures is needed when determining the sample size. However, calculated intra-CVs based on bioequivalence results of identical generic drugs produce different estimates. In this study, we collected bioequivalence results using public resources from the Ministry of Food and Drug Safety (MFDS) and calculated the intra-CVs of various generics. For the generics with multiple bioequivalence results, pooled intra-CVs were calculated. The estimated intra-CVs of 142 bioequivalence studies were 14.7±8.2% for AUC and 21.7±8.8% for Cmax. Intra-CVs of Cmax were larger than those of area under the concentration-time curve (AUC) in 129 studies (90.8%). For the 26 generics with multiple bioequivalence results, the coefficients of variation of intra-CVs between identical generics (mean±sd (min ~ max)) were 38.0±24.4% (1.9 ~ 105.3%) for AUC and 27.9±18.2% (4.0 ~ 70.1%) for Cmax. These results suggest that substantial variation exists among the bioequivalence results of identical generics. In this study, we presented the intra-CVs of various generics with their pooled intra-CVs. The estimated intra-CVs calculated in this study will provide useful information for planning future bioequivalence studies. (This is republication of the article 'Transl Clin Pharmacol 2017;25:179-182' retracted from critical typographic errors. See the 'Retraction and Republication section of this issue for further information)


Subject(s)
Area Under Curve , Cross-Over Studies , Drugs, Generic , Sample Size , Therapeutic Equivalency
12.
Article in English | WPRIM | ID: wpr-742395

ABSTRACT

This study aimed to compare the pharmacokinetics of fixed-dose combination (FDC) tablet of rosuvastatin 20 mg/ezetimibe 10 mg with that of concurrent administration of individual rosuvastatin 20 mg tablet and ezetimibe 10 mg tablet in healthy subjects. A randomized, open label, single-dose, two-way crossover study was conducted. Subjects randomly received test formulation (FDC tablet of rosuvastatin 20 mg/ezetimibe 10 mg) or reference formulation (co-administration of rosuvastatin 20 mg tablet and ezetimibe 10 mg tablet). After 2 weeks of washout, subjects received the other treatment. Blood samples were collected up to 72 hours post-dose in each period. Plasma concentrations of rosuvastatin, ezetimibe and total ezetimibe (ezetimibe + ezetimibe glucuronide) were analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The geometric mean ratio (GMR) of Cmax and AUClast (90% confidence interval, CI) for rosuvastatin was 1.036 (0.979–1.096) and 1.024 (0.981–1.070), respectively. The corresponding values for ezetimibe were 0.963 (0.888–1.043) and 1.021 (0.969–1.074), respectively. The corresponding values for total ezetimibe were 0.886 (0.835–0.940) and 0.983 (0.946–1.022), respectively. FDC tablet containing rosuvastatin 20 mg and ezetimibe 10 mg is bioequivalent to the co-administration of commercially available individual tablets of rosuvastatin and ezetimibe as GMR with 90% CI of Cmax and AUClast of rosuvastatin, ezetimibe and total ezetimibe were contained within conventionally accepted bioequivalence criteria.


Subject(s)
Cross-Over Studies , Ezetimibe , Healthy Volunteers , Mass Spectrometry , Pharmacokinetics , Plasma , Rosuvastatin Calcium , Tablets , Therapeutic Equivalency
13.
Article in English | WPRIM | ID: wpr-742394

ABSTRACT

Metformin, an oral antihyperglycemic agent, is widely used as the first-line pharmacotherapy for type 2 diabetes mellitus (T2DM). It has been in use for several decades as numerous different formulations. However, despite its use, population pharmacokinetic (PK) modeling of metformin is not well developed. The aim of the present study was to evaluate the effect of formulation on PK parameters by developing a population PK model of metformin in Koreans and using this model to assess bioequivalence. We used a comparative PK study of a single agent and a fixed-dose combination of metformin in 36 healthy volunteers. The population PK model of metformin was developed using NONMEM (version 7.3). Visual predictive checks and bootstrap methods were performed to determine the adequacy of the model. The plasma concentration-time profile was best described by a two-compartment, first-order elimination model with first-order absorption followed by zeroorder absorption with lag time. From the covariate analysis, formulation had significant effect (p < 0.01) on relative bioavailability (F = 0.94) and first-order absorption constant (Ka = 0.83), but the difference was within the range of bioequivalence criteria. No other covariate was shown to have significant effect on PK parameters. The PK profile of the disposition phase was consistent with the published literature. However, in the present study, the multiple peaks found during the absorption phase implied the possible diversity of absorption PK profile depending on formulation or population. Unlike traditional bioequivalence analysis, the population PK model reflects formulation differences on specific parameters and reflected simulation can be performed.


Subject(s)
Absorption , Adult , Biological Availability , Diabetes Mellitus, Type 2 , Drug Therapy , Healthy Volunteers , Humans , Metformin , Pharmacokinetics , Plasma , Therapeutic Equivalency
14.
Gastroenterol. latinoam ; 29(supl.1): S68-S72, 2018. tab, ilus
Article in Spanish | LILACS | ID: biblio-1117874

ABSTRACT

Biological therapies have been essential for the management of inflammatory bowel disease; however, their high cost results in many patients being unable to access them. With time, commercial patents of many "original" biologics are reaching or almost in the point of reaching the expiration date of their licenses, which has allowed for the development of new agents known as biosimilars leading to a reduction of the cost of these therapies. The objective of this review is to explain what biosimilars are and show evidence of their effectiveness and safety.


Las terapias biológicas son parte fundamental en el manejo de la enfermedad inflamatoria intestinal, sin embargo los costos de éstas han hecho que muchos de los pacientes que tienen indicación de su uso, no puedan utilizarlas. Con el paso del tiempo, muchos biológicos "originales" están alcanzando o a punto de alcanzar el vencimiento de sus patentes, lo que ha llevado al desarrollo de nuevos agentes conocidos como biosimilares, determinando una disminución en los costos de estas terapias. Esta revisión tiene como objetivo explicar en qué consisten los biosimilares y la evidencia actual con respecto a su eficacia y seguridad.


Subject(s)
Humans , Inflammatory Bowel Diseases/drug therapy , Biosimilar Pharmaceuticals/therapeutic use , Therapeutic Equivalency , Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Chile , Interchange of Drugs
15.
Braz. J. Pharm. Sci. (Online) ; 54(4): e17239, 2018. tab, graf
Article in English | LILACS | ID: biblio-1001562

ABSTRACT

A liquid chromatography method was developed and validated for the determination of gemifloxacin in human plasma using chloramphenicol as internal standard to achieve lower quantification limit. Acetonitrile was used to precipitated and extracted analyte and internal standard from plasma by Protein Precipitation. Analysis was performed isocratically on C18 column using 25% acetonitrile and 75% 0.02 M phosphate buffer as mobile phase. The method was demonstrated to be linear from 0.003 µg/mL to 5 µg/mL with the lower limit of quantitation of 0.003 µg/mL. The method was successfully applied for the bioequivalence study of gemifloxacin after a single oral administration of 320 mg gemifloxacin mesylate tablets to 12 healthy volunteers.


Subject(s)
Humans , Male , Female , Adult , Therapeutic Equivalency , Chromatography, High Pressure Liquid/instrumentation , /analysis , /pharmacokinetics , Plasma , Ultraviolet Rays
16.
Mem. Inst. Oswaldo Cruz ; 113(12): e180279, 2018. tab
Article in English | LILACS | ID: biblio-976232

ABSTRACT

BACKGROUND The main strategy to control human malaria still relies on specific drug treatment, limited now by Plasmodium falciparum-resistant parasites, including that against artemisinin derivatives. Despite the large number of active compounds described in the literature, few of them reached full development against human malaria. Drug repositioning is a fast and less expensive strategy for antimalarial drug discovery, because these compounds are already approved for human use. OBJECTIVES To identify new antimalarial drugs from compounds commercially available and used for other indications. METHODS Accuvit®, Ginkgo® and Soyfit®, rich in flavonoids, and also the standard flavonoids, hesperidin, quercetin, and genistein were tested against blood cultures of chloroquine-resistant P. falciparum, as well as chloroquine, a reference antimalarial. Inhibition of parasite growth was measured in immunoenzymatic assay with monoclonal anti-P. falciparum antibodies, specific to the histidine-rich protein II. Tests in mice with P. berghei malaria were based on percent of parasitaemia reduction. These compounds were also evaluated for in vitro cytotoxicity. FINDINGS The inhibition of parasite growth in vitro showed that Accuvit® was the most active drug (IC50 5 ± 3.9 μg/mL). Soyfit® was partially active (IC50 13.6 ± 7.7 μg/mL), and Ginkgo® (IC50 38.4 ± 14 μg/mL) was inactive. All such compounds were active in vivo at a dose of 50 mg/kg body weight. Accuvit® and quercetin induced the highest reduction of P. berghei parasitaemia (63% and 53%, respectively) on day 5 after parasite inoculation. As expected, the compounds tested were not toxic. MAIN CONCLUSIONS The antimalarial activity of Accuvit® was not related to flavonoids only, and it possibly results from synergisms with other compounds present in this drug product, such as multivitamins. Multivitamins in Accuvit® may explain its effect against the malaria parasites. This work demonstrated for the first time the activity of these drugs, which are already marketed.


Subject(s)
Humans , Flavonoids/pharmacology , Drug Resistance , Therapeutic Equivalency , Chloroquine/therapeutic use , Malaria/complications , Plasmodium falciparum , Proprietary Drug Name
17.
Psicol. Educ. (Online) ; (45): 11-20, dez. 2017. tab, ilus
Article in Portuguese | LILACS | ID: biblio-996506

ABSTRACT

A literatura da área de Análise do Comportamento tem mostrado contínuas evidências de que programas de ensino baseados no paradigma de equivalência de estímulos são eficazes no ensino de diferentes habilidades acadêmicas tanto em crianças de desenvolvimento típico quanto em crianças com atrasos de desenvolvimento. O procedimento informatizado de escolha-de-acordo-com-o-modelo (MTS, em inglês) foi usado com sucesso, em estudos anteriores, para o ensino de habilidades matemáticas (por exemplo, uso de sistema monetário) para jovens com deficiência intelectual. Este estudo teve como objetivo avaliar a eficácia do ensino informatizado em tarefas de MTS, e desenvolver, aplicar e avaliar um currículo para ensino de conceito de número para crianças com TEA. Para o ensino do conceito de número, foi conduzido um treino gradual, usando como estímulos grupos de três numerais, em tarefas de MTS computadorizado para a formação das classes de 'numeral' e 'quantidade', relacionadas entre si. Participaram da pesquisa três alunos com TEA de oito a 12 anos de idade. Os resultados mostraram que o procedimento foi eficaz para todos os participantes, e que um dos três participantes adquiriu todo o repertório desejado em um total de 24 sessões de ensino.


The purposes of this research are to evaluate the effectiveness of MTS computerized teaching tasks, and develop, apply and evaluate a Stimulus Equivalence Paradigm based curriculum to teach number concept. Studies that used MTS procedure to teach arbitrary conditional discriminations and equivalence relations obtained positive results on subjects with disability. We propose a systematic replication of Rossit (2003), that used MTS tasks to teach monetary system to youths with intellectual disability on a Stimulus Equivalence Paradigm based organized curriculum. In order to teach number concept, the experimental stimuli (numerals from one until nine, and figures of non-representational forms) were divided in three stimuli groups of increasing values in a multiple baseline design among stimuli groups. Participants in the research were three ASD students, eight to 12 years old. The results show efficacy on teaching number concept for ASD children with strategy derived from Stimulus Equivalence, replicating the results obtained by Rossit (2003) and corroborating previous notes on the contribution of resource derived from the Applied Behavior Analysis for the success in including students with ASD. To teach the concept of number, a gradual training was conducted using as stimuli groups of three numerals, in tasks of computerized MTS for the formation of the 'numeral' and 'quantity' classes, related to each other. Three students with ASD from eight to 12 years old participated in the study. The results showed that the procedure was effective for all participants, and one of the three participants acquired the whole wanted repertoire in 24 teaching sessions.


La literatura sobre la conducta en Análisis de la Conducta evidencia que programas de educación basados en el paradigma de la equivalencia de estímulos son eficaces en la enseñanza de diversas habilidades académicas, en niños con desarrollo típico y niños con retrasos en el desarrollo. El procedimiento informatizado de elecciónde-acuerdo-con-modelo (MTS, en Inglés) se ha utilizado con éxito en estudios previos para la educación de habilidades matemáticas (por ejemplo, utilizar el sistema monetario) para los jóvenes con discapacidad intelectual. Este estudio tuvo como objetivo evaluar la eficacia de la enseñanza informatizada en las tareas de MTS, desarrollar, implementar y evaluar un currículo para la enseñanza de conceptos numéricos para niños con TEA. Para la enseñanza del concepto de número, un entrenamiento gradual se llevó a cabo, utilizando como estímulos grupos de tres números en tareas MTS informatizados para la formación de la clase "número" y "cantidad" vinculado. Los participantes fueron tres estudiantes con TEA de ocho a 12 años de edad. Los resultados mostraron que el procedimiento fue efectivo para todos los participantes, y que uno de los tres participantes adquirió todo el repertorio deseado en un total de 24 sesiones de enseñanza. señanza.


Subject(s)
Humans , Child , Autistic Disorder , Therapeutic Equivalency , Child , Mathematics/education
18.
Anon.
Prensa méd. argent ; 103(10): 553-555, 20170000. tab
Article in English | LILACS, BINACIS | ID: biblio-1371607

ABSTRACT

All plasma concentrations of subject no. 35 in period II were below the quantification (BLQ ). As there were no significant clinical observations, data 35 were considered for pharmacokinetic and statistical analysis. Hence, data were considered for pharmacokinetic and statistical analysis. However, analysis was also performed excluding subject no. 35 for information purpose. The 90 % confidence intervals of Lntransformed parameters for Monomethyl fumarate are summarized below ; Safety results A total of eight (08) adverse events were reported during the clinical phase of the study, of which four (04) adverse event were probably related to the study drug, three (03) adverse events were unrelated and one (01) adverse event was possibly related to the drug. All the adverse events were mild to moderate in severity and were resolved. No serious adverse events were observed during the study periods. Conclusion Bioequivalence between Test Product: Dimethyl fumarate 240 mg modified release capsules (manufacturer: Rider Synthon Ltda, Chile) and reference Product: Tecfidera® 240 mg gastroresistant hard capsules (MAH: Biogen Idec. Ltd., United Kingdom) was demonstrated in this study


Subject(s)
Humans , Adult , Capsules/pharmacokinetics , Therapeutic Equivalency , Randomized Controlled Trials as Topic , Follow-Up Studies , Period Effect , Dimethyl Fumarate/administration & dosage , Dimethyl Fumarate/adverse effects
19.
Prensa méd. argent ; 103(7): 427-432, 20170000. tab, graf
Article in English | LILACS, BINACIS | ID: biblio-1372869

ABSTRACT

Conclusion Bioequivalence Results: A total of 40 subjects were planned and enrolled in the study. Thirty-nine (39) subjects completed the clinical phase of the study and data of thirty-nine (39) subjects were considered for pharmacokinetic and statistical analysis. The 90 % CI's of Ln-transformed parameters for Fingolimod are summarized below: Safety results: Two (02) AEs were reported during the clinical phase of the study which were unexpected and not related to study drug, mild in severity and were considered for lost to follow up. No serious AEs (SAEs) were observed during the clinical phase. Conclusion: Based on the statistical analysis of Fingolimod on 39 subjects, it is concluded that the Test Product (T): Fibroneurina manufactured by Laboratorios Bagó, Argentina shows bioequivalence with the Reference Product Fingolimod 0.5 mg hard capsules Manufactured by Novartis Pharma GmbH, Germany. Date of the report: 04 February 2017


Subject(s)
Humans , Capsules/therapeutic use , Therapeutic Equivalency , Statistical Analysis , Fingolimod Hydrochloride/therapeutic use
20.
Prensa méd. argent ; 103(9): 502-506, 20170000. tab, graf
Article in English | LILACS, BINACIS | ID: biblio-1372014

ABSTRACT

Conclusion Bioequivalence Results: A total of 40 subjects were planned and enrolled in the study. Thirty-nine (39) subjects completed the clinical phase of the study and data of thirty-nine (39) subjects were considered for pharmacokinetic and statistical analysis. The 90 % CI's of Ln-transformed parameters for Fingolimod are summarized below: Safety results: Two (02) AEs were reported during the clinical phase of the study which were unexpected and not related to study drug, mild in severity and were considered for lost to follow up. No serious AEs (SAEs) were observed during the clinical phase. Conclusion: Based on the statistical analysis of Fingolimod on 39 subjects, it is concluded that the Test Product (T): Fibroneurina manufactured by Laboratorios Bagó, Argentina shows bioequivalence with the Reference Product Fingolimod 0.5 mg hard capsules Manufactured by Novartis Pharma GmbH, Germany. Date of the report: 04 February 2017


Subject(s)
Humans , Capsules/pharmacokinetics , Therapeutic Equivalency , Previous Analysis of Products , Fingolimod Hydrochloride/administration & dosage
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