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Effect of gemfibrozil on the pharmacokinetics of pioglitazone

  • Pharmacokinetics and Disposition
  • Published:
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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 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.

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Authors and Affiliations

  1. Clinical Pharmaceutical Research Institute, The Second Xiangya Hospital, The Central South University, Changsha, 410011, China

    Li-Jing Deng, Feng Wang & Huan-De Li

  2. Clinical Pharmaceutical Institute, Pharmaceutical Department, The First Affiliated Hospital of Nanhua University, Hengyang, China

    Li-Jing Deng

Authors
  1. Li-Jing Deng
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  2. Feng Wang
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  3. Huan-De Li
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Correspondence to Huan-De Li.

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Deng, LJ., Wang, F. & Li, HD. Effect of gemfibrozil on the pharmacokinetics of pioglitazone. Eur J Clin Pharmacol 61, 831–836 (2005). https://doi.org/10.1007/s00228-005-0042-6

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  • DOI: https://doi.org/10.1007/s00228-005-0042-6

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