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Effects of Lovastatin on the Pharmacokinetics of Verapamil and its Active Metabolite, Norverapamil in Rats: Possible Role of P-glycoprotein Inhibition by Lovastatin
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  • Effects of Lovastatin on the Pharmacokinetics of Verapamil and its Active Metabolite, Norverapamil in Rats: Possible Role of P-glycoprotein Inhibition by Lovastatin
  • Effects of Lovastatin on the Pharmacokinetics of Verapamil and its Active Metabolite, Norverapamil in Rats: Possible Role of P-glycoprotein Inhibition by Lovastatin
저자명
Hong. Soon-Py,Chang. Kyoung-Sig,Koh. Young-Youp,Choi. Dong-Hyun,Choi. Jun-Shik
간행물명
Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea
권/호정보
2009년|32권 10호|pp.1447-1452 (6 pages)
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대한약학회
파일정보
정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
서지반출

기타언어초록

This study was to investigate the effect of lovastatin on the bioavailability or pharmacokinetics of verapamil and its major metabolite, norverapamil, in rats. The pharmacokinetic parameters of verapamil and norverapamil in rats were measured after the oral administration of verapamil (9 mg/kg) in the presence or absence of lovastatin (0.3 or 1.0 mg/kg). The pharmacokinetic parameters of verapamil were significantly altered by the presence of lovastatin compared to the control group (given verapamil alone). The presence of lovastatin significantly (p < 0.05, 0.3 mg/kg; p < 0.01, 1.0 mg/kg) increased the total area under the plasma concentration-time curve (AUC) of verapamil by 26.5-64.8%, and the peak plasma concentration ($C_{max}$) of verapamil by 34.1-65.9%. Consequently, the relative bioavailability (R.B.) of verapamil was increased by 1.27- to 1.65-fold than that of the control group. However, there was not significant change in the time to reach the peak plasma concentration ($T_{max}$) and the terminal half-life ($t_{1/2}$) of verapamil in the presence of lovastatin. The AUC and $C_{max}$ of norverapamil were significantly (p < 0.05) higher than those of presence of 1.0 mg/kg of lovastatin compared with the control group. However, there was no significant change in the metabolite-parent ratio (M.R.) of norverapamil in the presence of lovastatin. The presence of lovastatin significantly enhanced the oral bioavailability of verapamil. The enhanced oral bioavailability of verapamil may be due to inhibition both of the CYP3A-mediated metabolism and the efflux pump P-glycoprotein (P-gp) in the intestine and/or in liver by the presence of lovastatin.