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

• Published in: European journal of clinical pharmacology Vol. 74; no. 5; pp. 561 - 569
• Main Authors: Sangle, Ganesh V., Patil, Mohan, Deshmukh, Nitin J., Shengule, Sushant A., Kamble, Shantibhushan, Vuppalavanchu, Kiran Kumar, Kale, Sushil, Baig, Mirza Layeeq Ahmed, Singh, Geetchandra, Shaikh, Javed, Tripathi, Jitendra, Aravindababu, P.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-05-2018; Springer Nature B.V
• Subjects: Asian people; Bioavailability; Biomedical and Life Sciences; Biomedicine; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Glucagon; Glucagon-like peptide 1; Inhibition; Insulin; Males; Peptidase; Pharmacodynamics; Pharmacokinetics; Pharmacology/Toxicology; Incretins; DPP-IV inhibitors; Sitagliptin; Pharmacodynamics; Pharmacokinetics
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-018-2433-5

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 (
C
max
,
T
max
, AUC
0-∞
and
t
1/2
) 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
C
max
491.7 (135.9) ng/mL; AUC
0-∞
4256.1 (509.9) ng· hr/mL,
T
max
2.9 (1.0) hr and
t
1/2
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.