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Effect of Pioglitazone on the Pharmacokinetics of Verapamil and Its Major Metabolite, Norverapamil, in Rats
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  • Effect of Pioglitazone on the Pharmacokinetics of Verapamil and Its Major Metabolite, Norverapamil, in Rats
  • Effect of Pioglitazone on the Pharmacokinetics of Verapamil and Its Major Metabolite, Norverapamil, in Rats
저자명
Choi. Jon-Shik,Burm. Jin-Pil
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
권/호정보
2008년|31권 9호|pp.1200-1204 (5 pages)
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대한약학회
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정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

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 ($C_{max}$) 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.