Effect of gemfibrozil on the pharmacokinetics of pioglitazone

Eur J Clin Pharmacol. 2005 Dec;61(11):831-6. doi: 10.1007/s00228-005-0042-6. Epub 2005 Nov 8.


Objective: Our objective was to study the effects of gemfibrozil on the pharmacokinetics of pioglitazone and the active compounds, which are all the substrates of CYP2C8 and CYP3A4.

Methods: In a randomized, two-phase crossover study, 10 healthy volunteers were pretreated for 2 days with either 600 mg oral gemfibrozil or placebo twice daily. On day 3, they received a single dose of 600 mg gemfibrozil or placebo, and 1 h later they received a single oral dose of 30 mg pioglitazone. Plasma concentrations of pioglitazone and both active metabolites M-III and M-IV were measured for up to 120 h.

Results: Gemfibrozil raised the mean total area under the concentration-time curve (AUC) of parent pioglitazone 3.4-fold (P<0.001). No statistically significant changes were seen in the total AUC of M-III or M-IV after gemfibrozil pretreatment. Gemfibrozil reduced the M-III/pioglitazone and M-IV/pioglitazone AUC(0-infinity) ratio by 71% (P<0.001) and 65%(P<0.001), strikingly prolonging their t((1/2)).

Conclusion: Gemfibrozil greatly increased the plasma concentration of parent pioglitazone and also inhibited the further metabolism of M-III and M-IV. Careful blood glucose monitoring and dosage adjustments are suggested during coadministration of pioglitazone and gemfibrozil.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Area Under Curve
  • Cross-Over Studies
  • Drug Interactions
  • Gemfibrozil / pharmacology*
  • Half-Life
  • Humans
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypolipidemic Agents / pharmacology*
  • Male
  • Pioglitazone
  • Thiazolidinediones / metabolism
  • Thiazolidinediones / pharmacokinetics*


  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Thiazolidinediones
  • Gemfibrozil
  • Pioglitazone