Evaluation of pharmacokinetic and pharmacodynamic parameters following single dose of sitagliptin in healthy Indian males.

ABSTRACT

PURPOSE: Sitagliptin, a dipeptidyl peptidase (DPP)-IV inhibitor approved for the treatment of type 2 diabetes, is reported to be more efficacious in Indian patients than non-Indian patient population. The objective of the study was to evaluate pharmacokinetic and pharmacodynamic (PK/PD) parameters of single-dose sitagliptin 100 mg (Januvia) in healthy Indian male participants. METHOD: In a randomised, single-dose, open-label, three-treatment, three-period, three-sequence, crossover bioavailability study, 18 healthy male participants received single-dose of sitagliptin under fasted and fed conditions. PK parameters (Cmax, Tmax, AUC0-∞ and t1/2) were determined using Phoenix WinNonlin software. PD parameters [DPP-IV inhibition, active glucagon-like peptide-1 (GLP-1) and insulin] were determined using established methods. RESULTS: PK parameters expressed in mean (SD) were Cmax 491.7 (135.9) ng/mL; AUC0-∞ 4256.1 (509.9) ng· hr/mL, Tmax 2.9 (1.0) hr and t1/2 10.4 (3.0) hr. The weighted average (WA) plasma DPP-4 inhibition over 24 h was 89.6% and WA of plasma active GLP-1 over 2 h after standardised meal (geometric mean ratio) was 11.1 (9.9) pM/L which is two- to- four fold higher compared to that reported in other populations. The mean average (SD) AUC of plasma insulin over 2 h of standardised meal was 47.9 (24.9) µIU/mL. CONCLUSION: Although, there are differences in pharmacokinetic parameters, no clinically meaningful differences were observed with respect to DPP-IV inhibition between Indian and non-Indian population.