Archives of Pharmacal Research

, Volume 31, Issue 9, pp 1200–1204 | Cite as

Effect of pioglitazone on the pharmacokinetics of verapamil and its major metabolite, norverapamil, in rats

  • Jun Shik Choi
  • Jin Pil Burm
Research Articles Drug Development


Pioglitazone, a thiazolidinedione antidiabetic drug, inhibits cytochrome P450 (CYP) 2C8 and CYP3A4 enzymes in vitro. This study investigated the effect of pioglitazone on the pharmacokinetics of verapamil and its major metabolite, norverapamil, in rats, after oral administration of verapamil (9 mg/kg) in the presence or absence of pioglitazone (0.3 or 1.0 mg/kg). Pioglitazone altered verapamil pharmacokinetics compared with verapamil alone. The presence of 1.0 mg/kg of pioglitazone significantly (p < 0.05) increased the area under the plasma concentration-time curve (AUC) and the peak concentration (Cmax) of verapamil by 49.0% and 46.8%, respectively, and significantly (p < 0.05) decreased the total plasma clearance (CL/F) of verapamil by 32.8%. The metabolite-parent AUC ratio in the presence of pioglitazone (1.0 mg/kg) significantly (p < 0.05) decreased by 21.9% compared to the control group. Thus, coadministration of pioglitazone inhibited the CYP3A4-mediated metabolism of verapamil.

Key words

Verapamil Norverapamil Pioglitazone Pharmacokinetics CYP3A4 


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Copyright information

© The Pharmaceutical Society of Korea 2008

Authors and Affiliations

  1. 1.College of PharmacyChosun UniversityGwangjuKorea
  2. 2.Chosun Nursing CollegeGwangjuKorea

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