Browsing by Author "Uang Y.-S."

Red yeast rice (RYR) can reduce cholesterol through its active component, lovastatin. This study was to investigate the pharmacokinetic properties of lovastatin in RYR products and potential RYR-drug interactions. Extracts of three registered RYR products (LipoCol Forte, Cholestin, and Xuezhikang) were more effective than pure lovastatin in inhibiting the activities of cytochrome P450 enzymes and P-glycoprotein. Among CYP450 enzymes, RYR showed the highest inhibition on CYP1A2 and CYP2C19, with comparable inhibitory potencies to the corresponding typical inhibitors. In healthy volunteers taking the RYR product LipoCol Forte, the pharmacokinetic properties of lovastatin and lovastatin acid were linear in the dose range of 1 to 4 capsules taken as a single dose and no significant accumulation was observed after multiple dosing. Concomitant use of one LipoCol Forte capsule with nifedipine did not change the pharmacokinetics of nifedipine. Yet, concomitant use of gemfibrozil with LipoCol Forte resulted in a significant increase in the plasma concentration of lovastatin acid. These findings suggest that the use of RYR products may not have effects on the pharmacokinetics of concomitant comedications despite their effects to inhibit the activities of CYP450 enzymes and P-gp, whereas gemfibrozil affects the pharmacokinetics of lovastatin acid when used concomitantly with RYR products. Copyright ? 2012 Chia-Hao Chen et al.

Study Objectives. To determine the pharmacokinetic and pharmacodynamic rationale for the optimum regimen of rabeprazole in the treatment of Helicobacter pylori infection in patients who are cytochrome P450 (CYP) 2C19 poor metabolizers or extensive metabolizers. Design. Prospective, multiple-dose pharmacokinetic and pharmacodynamic study. Setting. University-affiliated medical center in Taiwan. Subjects. Twelve healthy volunteers (aged 20-30 yrs) who were identified as CYP2C19 poor metabolizers (six subjects) or extensive metabolizers (six). Intervention. Each subject received rabeprazole 20 mg twice/day for 3 consecutive days and once/day on the fourth day. Measurements and Main Results. Pharmacokinetic and pharmacodynamic parameters were compared between CYP2C19 poor and extensive metabolizers on day 1 and day 4 of dosing. The mean ± SD values of area under the concentration-time curve of rabeprazole and rabeprazole thioether were significantly higher in poor metabolizers than in extensive metabolizers on day 1 (5357 ± 883 vs 1131 ± 512 ng?hr/ml and 1703 ± 432 vs 561 ± 358 ng?hr/ml, respectively; p<0.001) and on day 4 (5601 ± 669 vs 1619 ± 778 ng?hr/ml and 1914 ± 378 vs 511 ± 360 ng?hr/ml, respectively; p<0.001). However, no significant difference was noted between day 1 and day 4 of dosing within the same genotype groups. Only CYP2C19 poor metabolizers had significantly higher plasma gastrin levels on day 4 compared with those levels on day 1 (p<0.05). The pharmacokinetic-pharmacodynamic relationship of rabeprazole appears to be time dependent. Conclusion. The pharmacokinetic and pharmacodynamic data suggest that CYP2C19 poor metabolizers might be subject to advantageous conditions, especially after day 4, for treating H. pylori infection with rabeprazole.