European Journal of Clinical Pharmacology

, Volume 61, Issue 11, pp 831–836

Effect of gemfibrozil on the pharmacokinetics of pioglitazone

Pharmacokinetics and Disposition

DOI: 10.1007/s00228-005-0042-6

Cite this article as:
Deng, LJ., Wang, F. & Li, HD. Eur J Clin Pharmacol (2005) 61: 831. doi:10.1007/s00228-005-0042-6



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.


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.


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.


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.


Gemfibrozil Pioglitazone Pharmacokinetic Inhibit 

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Clinical Pharmaceutical Research Institute, The Second Xiangya HospitalThe Central South UniversityChangshaChina
  2. 2.Clinical Pharmaceutical Institute, Pharmaceutical DepartmentThe First Affiliated Hospital of Nanhua UniversityHengyangChina

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