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), AUC(0-∞) (3,621 ± 222.5 vs. 5,574 ± 249.6 ng h/ml; p < 0.0002), C(max) (282.9 ± 7.7 vs. 344.1 ± 5.9 ng/ml; p < 0.0001), and t(½) (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.
RCT Entities:
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 gemfibrozilas 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), AUC(0-∞) (3,621 ± 222.5 vs. 5,574 ± 249.6 ng h/ml; p < 0.0002), C(max) (282.9 ± 7.7 vs. 344.1 ± 5.9 ng/ml; p < 0.0001), and t(½) (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 assitagliptin has a wide therapeutic index. Hence, in clinical practice, sitagliptin as 100 mg tablets and gemfibrozilas 600 mg tablets may be co-prescribed without much threat of sitagliptintoxicity. 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/humanorganic anion transporter-3 inhibitors. Further studies are needed to confirm these results in patients.
Authors: Xiao-Yan Chu; Kelly Bleasby; Jocelyn Yabut; Xiaoxin Cai; Grace Hoyee Chan; Michael J Hafey; Shiyao Xu; Arthur J Bergman; Matthew P Braun; Dennis C Dean; Raymond Evers Journal: J Pharmacol Exp Ther Date: 2007-02-21 Impact factor: 4.030
Authors: M Alba; D Sheng; Y Guan; D Williams-Herman; P Larson; J R Sachs; N Thornberry; G Herman; K D Kaufman; B J Goldstein Journal: Curr Med Res Opin Date: 2009-10 Impact factor: 2.580
Authors: Arthur J Bergman; Catherine Stevens; YanYan Zhou; Bingming Yi; Martine Laethem; Marina De Smet; Karen Snyder; Deborah Hilliard; Wesley Tanaka; Wei Zeng; Michael Tanen; Amy Q Wang; Li Chen; Gregory Winchell; Michael J Davies; Steven Ramael; John A Wagner; Gary A Herman Journal: Clin Ther Date: 2006-01 Impact factor: 3.393