title: Effect of gemfibrozil on the pharmacokinetics of pioglitazone.
abstract: 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)).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, The Central South University, Changsha 410011, China. denglijing7117@163.com
authors.forename: Li-Jing
authors.initials: LJ
authors.lastname: Deng
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Huan-De
authors.initials: HD
authors.lastname: Li
mesh_terms: D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D015248:Gemfibrozil / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D045162:Thiazolidinediones; D015248:Gemfibrozil; D000077205:Pioglitazone