Dataset Information

Evaluation of the highly variable agomelatine pharmacokinetics in Chinese healthy subjects to support bioequivalence study.

ABSTRACT:

Objectives

We aim to obtain the intra-subject coefficient of variability of a highly variable antidepressant agomelatine in humans, and propose an adjusted bioequivalence assessment strategy.

Methods

A single-dose, randomized crossover design was conducted in four periods (reference administered thrice, placebo administered once) separated by seven days. A validated LC-MS/MS assay was used to measure drug concentrations in serial blood samples.

Results

The intra-subject coefficient of variability was calculated using the residual variance of ANOVA analysis, and the results for Cmax and AUC0-t was 78.34% and 43.52%, respectively, in Chinese healthy subjects. The sample size required for standard BE study were 124(192, 340) if the expected deviation between the reference and generic products was set to 0 (5%, 10%).

Conclusions

Agomelatine meets the criteria for highly variable drug in Chinese healthy male subjects, and the traditional BE criteria for agomelatine needs to be adjusted to alleviate the resource and ethical burden of using a large numbers of subjects in clinical trials. Our clinical data on the intra-subject variability of agomelatine PK in Chinese healthy population enables to adjust bioequivalence (BE) assessment approach for agomelatine based on the RSABE approaches recommended by regulatory agencies.

Trial registration

ChiCTR.org ChiCTR-TTRCC-13003835.

SUBMITTER: Pei Q

PROVIDER: S-EPMC4203722 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Evaluation of the highly variable agomelatine pharmacokinetics in Chinese healthy subjects to support bioequivalence study.

Pei Qi Q Wang Yan Y Hu Zhe-Yi ZY Liu Shi-Kun SK Tan Hong-Yi HY Guo Cheng-Xian CX Zhang Ran-Ran RR Xiang Yu-Xia YX Huang Jie J Huang Lu L Yuan Hong H Yang Guo-Ping GP

PloS one 20141020 10

<h4>Objectives</h4>We aim to obtain the intra-subject coefficient of variability of a highly variable antidepressant agomelatine in humans, and propose an adjusted bioequivalence assessment strategy.<h4>Methods</h4>A single-dose, randomized crossover design was conducted in four periods (reference administered thrice, placebo administered once) separated by seven days. A validated LC-MS/MS assay was used to measure drug concentrations in serial blood samples.<h4>Results</h4>The intra-subject coe ...[more]

PMID: 25330096

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Dataset Information

Evaluation of the highly variable agomelatine pharmacokinetics in Chinese healthy subjects to support bioequivalence study.

Objectives

Methods

Results

Conclusions

Trial registration

Publications

Evaluation of the highly variable agomelatine pharmacokinetics in Chinese healthy subjects to support bioequivalence study.

Similar Datasets

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