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Pharmacokinetics and safety of highly variable valsartan in single-pill combination with amlodipine versus its generic formulation: a randomized, three-cycle, three-sequence, partially replicated crossover phase I bioequivalence clinical trial
Valsartan/amlodipine (I) is a single-pill combination (SPC) of an angiotensin II receptor blocker (ARB) and a calcium channel blocker (CCB) for treating hypertension. A clinical trial was performed to demonstrate that the test and reference valsartan/amlodipine formulations were bioequivalent under...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512707/ https://www.ncbi.nlm.nih.gov/pubmed/37745062 http://dx.doi.org/10.3389/fphar.2023.1264321 |
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author | Qiu, Bo Song, Haojing Ding, Congyang Sun, Xue Du, Runxuan Yang, Haotian Bai, Wanjun Dong, Zhanjun |
author_facet | Qiu, Bo Song, Haojing Ding, Congyang Sun, Xue Du, Runxuan Yang, Haotian Bai, Wanjun Dong, Zhanjun |
author_sort | Qiu, Bo |
collection | PubMed |
description | Valsartan/amlodipine (I) is a single-pill combination (SPC) of an angiotensin II receptor blocker (ARB) and a calcium channel blocker (CCB) for treating hypertension. A clinical trial was performed to demonstrate that the test and reference valsartan/amlodipine formulations were bioequivalent under fasting and postprandial conditions. Participants were randomly divided into three sequences at a ratio of 1:1:1 for three-cycle, reference formulation replicated, crossover administration. The average bioequivalence (ABE) and reference-scaled average bioequivalence (RSABE) methods were used to evaluate BE using the main pharmacokinetic (PK) parameters. Overall, 45 eligible participants were enrolled in the postprandial trial, which was consistent with the fasting trial. For valsartan, the RSABE method was used to evaluate the BE of C(max), while the ABE method was applied to evaluate the BE of AUC(0–t) and AUC(0–∞). Both point estimates and 95% upper confidence bound met the BE criteria. For amlodipine, the ABE method was performed, and the 90% confidence intervals of the geometric mean ratios (GMR) for C(max) and AUC(0–72 h) were all within 80%–125%, with the BE criteria being met. Therefore, the two formulations are bioequivalent and have similar safety profiles in healthy Chinese subjects. Clinical trial registration: [http://www.chinadrugtrials.org.cn/index.html], identifier [CTR20210214]. |
format | Online Article Text |
id | pubmed-10512707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105127072023-09-22 Pharmacokinetics and safety of highly variable valsartan in single-pill combination with amlodipine versus its generic formulation: a randomized, three-cycle, three-sequence, partially replicated crossover phase I bioequivalence clinical trial Qiu, Bo Song, Haojing Ding, Congyang Sun, Xue Du, Runxuan Yang, Haotian Bai, Wanjun Dong, Zhanjun Front Pharmacol Pharmacology Valsartan/amlodipine (I) is a single-pill combination (SPC) of an angiotensin II receptor blocker (ARB) and a calcium channel blocker (CCB) for treating hypertension. A clinical trial was performed to demonstrate that the test and reference valsartan/amlodipine formulations were bioequivalent under fasting and postprandial conditions. Participants were randomly divided into three sequences at a ratio of 1:1:1 for three-cycle, reference formulation replicated, crossover administration. The average bioequivalence (ABE) and reference-scaled average bioequivalence (RSABE) methods were used to evaluate BE using the main pharmacokinetic (PK) parameters. Overall, 45 eligible participants were enrolled in the postprandial trial, which was consistent with the fasting trial. For valsartan, the RSABE method was used to evaluate the BE of C(max), while the ABE method was applied to evaluate the BE of AUC(0–t) and AUC(0–∞). Both point estimates and 95% upper confidence bound met the BE criteria. For amlodipine, the ABE method was performed, and the 90% confidence intervals of the geometric mean ratios (GMR) for C(max) and AUC(0–72 h) were all within 80%–125%, with the BE criteria being met. Therefore, the two formulations are bioequivalent and have similar safety profiles in healthy Chinese subjects. Clinical trial registration: [http://www.chinadrugtrials.org.cn/index.html], identifier [CTR20210214]. Frontiers Media S.A. 2023-09-07 /pmc/articles/PMC10512707/ /pubmed/37745062 http://dx.doi.org/10.3389/fphar.2023.1264321 Text en Copyright © 2023 Qiu, Song, Ding, Sun, Du, Yang, Bai and Dong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Qiu, Bo Song, Haojing Ding, Congyang Sun, Xue Du, Runxuan Yang, Haotian Bai, Wanjun Dong, Zhanjun Pharmacokinetics and safety of highly variable valsartan in single-pill combination with amlodipine versus its generic formulation: a randomized, three-cycle, three-sequence, partially replicated crossover phase I bioequivalence clinical trial |
title | Pharmacokinetics and safety of highly variable valsartan in single-pill combination with amlodipine versus its generic formulation: a randomized, three-cycle, three-sequence, partially replicated crossover phase I bioequivalence clinical trial |
title_full | Pharmacokinetics and safety of highly variable valsartan in single-pill combination with amlodipine versus its generic formulation: a randomized, three-cycle, three-sequence, partially replicated crossover phase I bioequivalence clinical trial |
title_fullStr | Pharmacokinetics and safety of highly variable valsartan in single-pill combination with amlodipine versus its generic formulation: a randomized, three-cycle, three-sequence, partially replicated crossover phase I bioequivalence clinical trial |
title_full_unstemmed | Pharmacokinetics and safety of highly variable valsartan in single-pill combination with amlodipine versus its generic formulation: a randomized, three-cycle, three-sequence, partially replicated crossover phase I bioequivalence clinical trial |
title_short | Pharmacokinetics and safety of highly variable valsartan in single-pill combination with amlodipine versus its generic formulation: a randomized, three-cycle, three-sequence, partially replicated crossover phase I bioequivalence clinical trial |
title_sort | pharmacokinetics and safety of highly variable valsartan in single-pill combination with amlodipine versus its generic formulation: a randomized, three-cycle, three-sequence, partially replicated crossover phase i bioequivalence clinical trial |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10512707/ https://www.ncbi.nlm.nih.gov/pubmed/37745062 http://dx.doi.org/10.3389/fphar.2023.1264321 |
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