Effects of Sairei‐to on the pharmacokinetics of nifedipine in rats

Abstract

Sairei-to is a traditional herbal medicine used to complement, and as an alternative to, Western drugs. The aim of this study was to evaluate the pharmacokinetic interactions between Sairei-to and nifedipine (NFP), a substrate for CYP3A, in rats. NFP-oxidizing activity and the pharmacokinetics of NFP were examined after a single or 1-week of administration of Sairei-to (EK-114). NFP-oxidizing activity was enhanced transiently around 24 h after a single administration of EK-114 (1400 mg/kg). In vivo, the first-pass metabolism of NFP increased in the small intestine at 24 h after the administration of EK-114, and this effect disappeared at 72 h. Co-administration of EK-114 tended to inhibit the metabolism of NFP. On the other hand, when EK-114 was given at a high dose (1400 mg/kg) for 1 week, the oxidation of NFP in the small intestine was inhibited, and Cmax and AUC after the oral administration of NFP increased. In addition, a clinical dose of EK-114 (140 mg/kg) did not alter the pharmacokinetics of NFP, regardless of the administration schedule. EK-114 was suggested to affect the metabolism of NFP. However, the CYP3A-mediated pharmacokinetic interaction on the concomitant use of EK-114 may not be clinically significant.