Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects.
10.1016/j.apsb.2015.10.003
- Author:
Fang TANG
1
;
Rui ZHOU
1
;
Zeneng CHENG
1
;
Guoping YANG
2
;
Aiqiao CHEN
3
;
Zhi LIU
4
;
Hongyi TAN
2
;
Shuang YANG
2
;
Sanwang LI
1
;
Lingli MU
5
;
Peng YU
1
Author Information
1. School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
2. The Third Xiangya Hospital, Central South University, Changsha 410013, China.
3. School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
4. Hunan Tiger-Xiangya R&D Company Ltd., Changsha 410013, China.
5. Medical College, Hunan Normal University, Changsha 410006, China.
- Publication Type:Journal Article
- Keywords:
3-Hydroxy-agomelatine;
7-Desmethyl-agomelatine;
Agomelatine;
Chinese subjects;
Generic drug;
High variability;
Reference-scaled average bioequivalence
- From:
Acta Pharmaceutica Sinica B
2016;6(1):71-78
- CountryChina
- Language:English
-
Abstract:
The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios and ratio of geometric means (GMR) of AUC and C max of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and C max of 7-desmethyl-agomelatine and 3-hydroxy-agomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log-transformed ratios of C max, AUC0-t and AUC0-∞ of agomelatine (104.42-139.86, 101.33-123.83 and 97.90-117.94) were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55-123.03, 101.95-109.10 and 101.72-108.70) and 7-desmethyl-agomelatine (104.50-125.23, 102.36-111.50 and 101.62-110.64) were within the FDA bioequivalence definition intervals (0.80-1.25 for AUC and 0.75-1.33 for C max). The RSABE approach was successful in evaluating the bioequivalence of these two formulations.
