title: 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.
authors.affiliation: Department of Hospital Pharmacy, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Ikehata
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohnishi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kiyohara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maeda
authors.forename: Takuya
authors.initials: T
authors.lastname: Kawakita
authors.forename: Kohji
authors.initials: K
authors.lastname: Takara
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D004347:Drug Interactions; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004365:Drugs, Chinese Herbal; C080903:sairei-to; D009543:Nifedipine