Abstract
Purpose
To study the impact of gemfibrozil co-administration on the pharmacokinetics of sitagliptin in healthy Indian male volunteers.
Methods
A randomized open label two-period crossover study involving 12 healthy Indian male volunteers was conducted at a single center. In each phase, the volunteers were administered sitagliptin as 100 mg tablets, either alone or co-administered with gemfibrozil as 600 mg tablets twice daily for 3 days. There was a 2-week washout period between phases. The venous blood samples were serially collected at 0–12 h post-dose, and plasma concentrations of the study drugs were estimated by a validated high-performance liquid chromatography-ultraviolet method.
Results
Relative to the administration of sitagliptin alone, co-administration with gemfibrozil increased the AUC0-12 (2,167 ± 82.9 vs. 2,970 ± 76.4 ng h/ml; p < 0.0001), AUC0-∞ (3,621 ± 222.5 vs. 5,574 ± 249.6 ng h/ml; p < 0.0002), Cmax (282.9 ± 7.7 vs. 344.1 ± 5.9 ng/ml; p < 0.0001), and t½ (7.4 ± 0.6 vs. 10 ± 0.6 h; p = 0.0076) to statistically significant levels. The interindividual differences in the pharmacokinetic parameters of sitagliptin were found to be within acceptable limits (coefficient of variation <20%). No adverse drug events associated with sitagliptin occurred in the subjects during the study period.
Conclusion
Although the bioavailability of sitagliptin was increased by 54% when co-administered with gemfibrozil, this interaction may not have any clinical significance as sitagliptin has a wide therapeutic index. Hence, in clinical practice, sitagliptin as 100 mg tablets and gemfibrozil as 600 mg tablets may be co-prescribed without much threat of sitagliptin toxicity. However, these results may not hold if the dose of sitagliptin is increased or if is co-prescribed with other antidiabetic drugs and/or cytochrome P450 2C8/human organic anion transporter-3 inhibitors. Further studies are needed to confirm these results in patients.
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K. P., A., Meda, V.S., Kucherlapati, V.S.P.R. et al. Pharmacokinetic drug interaction between gemfibrozil and sitagliptin in healthy Indian male volunteers. Eur J Clin Pharmacol 68, 709–714 (2012). https://doi.org/10.1007/s00228-011-1177-2
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DOI: https://doi.org/10.1007/s00228-011-1177-2