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 AUC0–∞ ratio by 71% (P<0.001) and 65%(P<0.001), strikingly prolonging their t½.
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.
Keywords Gemfibrozil - Pioglitazone - Pharmacokinetic - Inhibit