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Metabolite Parameters as an Appropriate Alternative Approach for Assessment of Bioequivalence of Two Verapamil Formulations
A bioequivalence study of two verapamil formulations (generic verapamil tablets and Isoptin(®) tablets) was performed by comparing pharmacokinetic parameters of the parent drug and its major metabolite, norverapamil following a single dose administration of 80 mg verapamil hydrochloride in 22 health...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Shaheed Beheshti University of Medical Sciences
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157014/ https://www.ncbi.nlm.nih.gov/pubmed/25237334 |
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author | Haeri, Azadeh Javadian, Bahareh Saadati, Roonak Dadashzadeh, Simin |
author_facet | Haeri, Azadeh Javadian, Bahareh Saadati, Roonak Dadashzadeh, Simin |
author_sort | Haeri, Azadeh |
collection | PubMed |
description | A bioequivalence study of two verapamil formulations (generic verapamil tablets and Isoptin(®) tablets) was performed by comparing pharmacokinetic parameters of the parent drug and its major metabolite, norverapamil following a single dose administration of 80 mg verapamil hydrochloride in 22 healthy volunteers according to a randomized, two-period, crossover-design study. Moreover, the feasibility of proving bioequivalence of verapamil oral dosing form by means of norverapamil pharmacokinetic parameters was evaluated. Concentrations of verapamil and norverapamil were quantified in plasma using a validated high-performance liquid chromatography (HPLC) with fluorescence detection. The 90% CIs for the log-transformed ratios of verapamil C(max) (maximum plasma concentration) and AUC(0–∞)(area under the plasma concentration-versus-time curve from time zero to the infinity) were 73 to 101 and 80 to 103, respectively. Similarly, the corresponding ranges for norverapamil were 80-100 and 84-103, respectively. According to the parent drug data, the 90% confidence intervals around the geometric mean ratio of AUC happened to fit within preset bioequivalence limits of 80–125%, whereas those for C(max) did not. The 90% confidence intervals for both C(max) and AUC of norverapamil met preset bioequivalence limits. The AUC and C(max )of metabolite, when compared to parent drug, showed a much lower degree of variability and the 90% confidence intervals of the metabolite were therefore narrower than those of the parent drug. These observations indicate that bioequivalence studies using metabolite, norverapamil, could be a more suitable and preferable approach to assess bioequivalence of verapamil formulations due to its much lower variability and therefore lower number of volunteers that are required to conduct the study. |
format | Online Article Text |
id | pubmed-4157014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Shaheed Beheshti University of Medical Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-41570142014-09-18 Metabolite Parameters as an Appropriate Alternative Approach for Assessment of Bioequivalence of Two Verapamil Formulations Haeri, Azadeh Javadian, Bahareh Saadati, Roonak Dadashzadeh, Simin Iran J Pharm Res Original Article A bioequivalence study of two verapamil formulations (generic verapamil tablets and Isoptin(®) tablets) was performed by comparing pharmacokinetic parameters of the parent drug and its major metabolite, norverapamil following a single dose administration of 80 mg verapamil hydrochloride in 22 healthy volunteers according to a randomized, two-period, crossover-design study. Moreover, the feasibility of proving bioequivalence of verapamil oral dosing form by means of norverapamil pharmacokinetic parameters was evaluated. Concentrations of verapamil and norverapamil were quantified in plasma using a validated high-performance liquid chromatography (HPLC) with fluorescence detection. The 90% CIs for the log-transformed ratios of verapamil C(max) (maximum plasma concentration) and AUC(0–∞)(area under the plasma concentration-versus-time curve from time zero to the infinity) were 73 to 101 and 80 to 103, respectively. Similarly, the corresponding ranges for norverapamil were 80-100 and 84-103, respectively. According to the parent drug data, the 90% confidence intervals around the geometric mean ratio of AUC happened to fit within preset bioequivalence limits of 80–125%, whereas those for C(max) did not. The 90% confidence intervals for both C(max) and AUC of norverapamil met preset bioequivalence limits. The AUC and C(max )of metabolite, when compared to parent drug, showed a much lower degree of variability and the 90% confidence intervals of the metabolite were therefore narrower than those of the parent drug. These observations indicate that bioequivalence studies using metabolite, norverapamil, could be a more suitable and preferable approach to assess bioequivalence of verapamil formulations due to its much lower variability and therefore lower number of volunteers that are required to conduct the study. Shaheed Beheshti University of Medical Sciences 2014 /pmc/articles/PMC4157014/ /pubmed/25237334 Text en © 2014 by School of Pharmacy, Shaheed Beheshti University of Medical Sciences and Health Services This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Haeri, Azadeh Javadian, Bahareh Saadati, Roonak Dadashzadeh, Simin Metabolite Parameters as an Appropriate Alternative Approach for Assessment of Bioequivalence of Two Verapamil Formulations |
title | Metabolite Parameters as an Appropriate Alternative Approach for Assessment of Bioequivalence of Two Verapamil Formulations |
title_full | Metabolite Parameters as an Appropriate Alternative Approach for Assessment of Bioequivalence of Two Verapamil Formulations |
title_fullStr | Metabolite Parameters as an Appropriate Alternative Approach for Assessment of Bioequivalence of Two Verapamil Formulations |
title_full_unstemmed | Metabolite Parameters as an Appropriate Alternative Approach for Assessment of Bioequivalence of Two Verapamil Formulations |
title_short | Metabolite Parameters as an Appropriate Alternative Approach for Assessment of Bioequivalence of Two Verapamil Formulations |
title_sort | metabolite parameters as an appropriate alternative approach for assessment of bioequivalence of two verapamil formulations |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157014/ https://www.ncbi.nlm.nih.gov/pubmed/25237334 |
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