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

• Published in: Phytotherapy research Vol. 22; no. 1; pp. 12 - 17
• Main Authors: Ikehata, Mika, Ohnishi, Noriaki, Matsumoto, Tsuyoshi, Kiyohara, Yoshifumi, Maeda, Atsushi, Kawakita, Takuya, Takara, Kohji, Yokoyama, Teruyoshi
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.01.2008; Wiley
• Subjects: Animals; Biological and medical sciences; CYP3A; Drug Interactions; Drugs, Chinese Herbal - pharmacology; General pharmacology; Intestine, Small - drug effects; Intestine, Small - metabolism; Liver - drug effects; Liver - metabolism; Male; Medical sciences; nifedipine; Nifedipine - metabolism; Nifedipine - pharmacokinetics; Pharmacognosy. Homeopathy. Health food; pharmacokinetic interaction; Pharmacology. Drug treatments; Rats; Rats, Wistar; Sairei-to; traditional herbal medicine; pharmacokinetic interaction; Rat; Enzyme; Isozyme; Pharmacognosy; Cytochrome P450; Interaction; Calcium antagonist; Rodentia; Antiarrhythmic agent; Nifedipine; Medicinal plant; traditional herbal medicine; CYP3A; Vertebrata; Mammalia; Folk medicine; Sairei-to; Animal; Plant origin; Dihydropyridine derivatives; Pharmacokinetics
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.2234

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. Copyright © 2007 John Wiley & Sons, Ltd.