Effects of Kampo medicines on Cyp3a and P-glycoprotein activity in vivo

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In order to evaluate the possibility of Kampo medicines causing pharmacokinetic drug-drug interactions, the effects of 3 Kampo medicines (rikkunshito, yokukansan and boiogito) on the activities of cytochrome P450 (CYP) and P-glycoprotein (P-gp) were investigated in a mouse in vivo study using triazolam and digoxin, respectively, as probe substrates.<BR>A significant increase in the plasma triazolam concentration was observed by co-administration of ketoconazole, a Cyp3a inhibitor, whereas none of the Kampo medicines tested showed any significant effects on triazolam pharmacokinetics in mice. Similarly, plasma concentration of digoxin was significantly elevated by quinidine co-administration, while unaffected by any of the Kampo medicines investigated.<BR>These findings indicate that rikkunshito, yokukansan and boiogito are unlikely to affect the pharmacokinetics of co-administered drugs which are substrates of CYP3A and/or P-gp.

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