Inter- and Intra-individual Variability in the Pharmacokinetics of Agomelatine Tablets in Chinese Healthy Male...

Agomelatine is an antidepressant with a unique action mechanism differing from conventional antidepressants. The high inter- and intra-individual variability of agomelatine was previously reported, but no exact data values about the inter- and intra-individual variability in AUC and Cmax were mentioned. The current study aimed to determine and evaluate the inter- and intra-individual variability in AUC and Cmax of agomelatine tablets in Chinese healthy male subjects, providing useful information for designing bioequivalence studies of agomelatine. Each of 12 Chinese healthy male subjects received a 25-mg agomelatine tablet on 2 separate periods, and plasma samples were collected up to 24 h after dose and analyzed for agomelatine. Inter- and intra-individual variability in the pharmacokinetic parameters (Cmax, AUC0-t and AUC0-∞) of agomelatine was assessed. High variations in the plasma concentrations of agomelatine could be observed at each sampling time between the different subjects and in one subject on different periods. The inter-individual CVs of Cmax, AUC0-t and AUC0-∞ were 102.20%, 131.74% and 130.59%, respectively. The intra-individual CVs of Cmax, AUC0-t and AUC0-∞ were 84.34%, 49.61% and 50.83%, respectively. The results showed high inter- and intra-individual variability in the pharmacokinetics of agomelatine in Chinese healthy male subjects, and the intra-individual variability at CV>80% should be considered in the design of bioequivalence studies.