Related Experiment Video
Updated: Apr 21, 2026

An In Vitro Dissolution Determination of Multi-Index Components in Tibetan Medicine Rhodiola Granules
Published on: November 4, 2022
Evaluation of the highly variable agomelatine pharmacokinetics in Chinese healthy subjects to support bioequivalence
Qi Pei1, Yan Wang2, Zhe-Yi Hu3
1Department of pharmacy, the Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
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.
Related Concept Videos
Bioavailability Study Design: Healthy Subjects Versus Patients
Bioequivalence of Drugs: Drugs with Multiple Indications
Bioavailability Study Design: Single Versus Multiple Dose Studies
Bioequivalence Data: Statistical Interpretation
Pharmaceutical Alternatives: Polymorphic Form-Related and Particle Size-Related Therapeutic Nonequivalence
Bioequivalence studies: Biowaivers

