title: Pharmacokinetic drug interaction between gemfibrozil and sitagliptin in healthy Indian male volunteers.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacy Practice, JSS College of Pharmacy (A Constituent College of JSS University, Mysore), Ooty, 643001, The Nilgiris, Tamil Nadu, India. kparun@jsscpooty.org
authors.forename: Arun
authors.initials: A
authors.lastname: K P
authors.forename: Venkata Subbaiah
authors.initials: VS
authors.lastname: Meda
authors.forename: V S P Raj
authors.initials: VS
authors.lastname: Kucherlapati
authors.forename: Anil
authors.initials: A
authors.lastname: Dubala
authors.forename: Deepalakshmi
authors.initials: D
authors.lastname: M
authors.forename: Anand VijayaKumar
authors.initials: AV
authors.lastname: P R
authors.forename: Elango
authors.initials: E
authors.lastname: K
authors.forename: Suresh
authors.initials: S
authors.lastname: B
mesh_terms: D000328:Adult; D001682:Biological Availability; D018592:Cross-Over Studies; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D015248:Gemfibrozil / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D007194:India; D008297:Male; D008657:Metabolic Clearance Rate; D011719:Pyrazines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D000960:Hypolipidemic Agents; D011719:Pyrazines; D014230:Triazoles; D015248:Gemfibrozil; D000068900:Sitagliptin Phosphate