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Choi, Dong-Hyun,Li, Cheng,Choi, Jun-Shik Edifor] 2009 European journal of drug metabolism and pharmacoki Vol.34 No.3
<P>The aim of this study was to investigate the effect of simvastatin on the pharmacokinetics of verapamil and its major metabolite, norverapamil, in rats. The pharmacokinetic parameters of verapamil and norverapamil in rats were determined after the oral administration of verapamil (9 mg/kg) in the presence or absence of simvastatin (0.3 and 1.0 mg/kg). The pharmacokinetics of verapamil were significantly altered by the coadministration of simvastatin compared with those in the control group (given verapamil alone). The area under the plasma concentration-time curve (AUC) and the peak plasma concentration (Cmax) of verapamil were significantly increased (P < 0.05 at 0.3 mg/kg; P < 0.01 at 1.0 mg/kg) by simvastatin. Consequently, the absolute bioavailability (A.B.) of verapamil with simvastatin (7.3% at 0.3 mg/kg, 9.3% at 1.0 mg/kg) were significantly higher than those in the control group (P < 0.05, 5.2%). The AUC and Cmax of norverapamil were not significantly increased in the rats coadministered with simvastatin compared with those in the control group. Moreover, the metabolite-parent ratio (M.R.) of norverapamil were significantly decreased in rats coadministered with simvastatin. These results implied that simvastatin significantly enhanced the oral bioavailability of verapamil by inhibiting the CYP3A-mediated metabolism in small intestine or in the liver and P-glycoprotein (P-gp) efflux pump in small intestine. Therefore, concurrent use of verapamil and simvastatin should be monitored closely to potential drug interactions for safe therapy of cardiovascular diseases.</P>
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Yan, Yi-Dong,Marasini, Nirmal,Choi, Young Keun,Kim, Jong Oh,Woo, Jong Soo,Yong, Chul Soon,Choi, Han Gon Edifor] 2012 European journal of drug metabolism and pharmacoki Vol.37 No.3
<P>The present study investigated the effects of a curcumin self-emulsifying drug delivery systems (SEDDS) on the pharmacokinetics of orally administered docetaxel in rats. A single dose of docetaxel was orally administered (30 mg/kg) alone or after oral curcumin SEDDS (25, 50, 100 and 150 mg/kg) administration with time intervals of 0, 15 and 30 min, respectively. After oral administration, the C (max) and the area under the plasma concentration-time curve (AUC) of docetaxel were significantly increased (0 min, p < 0.05; 15 and 30 min, p < 0.01) by 2.2, 4.7 and 4.6 times and 2.0, 3.8 and 4.1 times compared to that of control group, respectively, after treatment with curcumin SEDDS (100 mg/kg) for each interval. Moreover, The C (max) of docetaxel was increased by 2.6 and 4.4 times in response to 25 and 50 mg/kg curcumin SEDDS treatment, respectively, the corresponding AUC was increased by about 2.4 and 3.1 times, and consequently the absolute bioavailabilities of docetaxel in these two treatment groups were 7.9 and 10.4%, respectively, which showed a significant increase of about 2.4- and 3.2-fold in comparison to the control value (3.3%). However, no further increase in either AUC or C (max) values of docetaxel was observed as the curcumin SEDDS dose was increased from 50 to 150 mg/kg. It is worth noting that the presence of curcumin SEDDS did not significantly decrease the systemic clearance, which was shown by the almost unchanged terminal half-life (t (1/2)) of docetaxel in all treatment groups. Thus, the enhanced bioavailability of oral docetaxel by curcumin SEDDS seemed to be likely due to an inhibition function of cytochrome P450 (CYP) 3A and P-glycoprotein (Pgp) in the intestines of the rats. However, further in vivo studies are needed to verify these hypotheses.</P>
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