A herbal-drug interaction study of keishi-bukuryo-gan, a traditional herbal preparation used for menopausal symptoms, in healthy female volunteers

Abstract

Abstract Objectives Many patients use herbal medicines to relieve menopausal symptoms. Keishi-bukuryo-gan contains five herbal components, and has been used for treating hypermenorrhoea, dysmenorrhoea and menopausal symptoms in Asian countries. In this study, we investigated the potential herb–drug interactions of keishi-bukuryo-gan in healthy female subjects. Methods Thirty-one healthy females (20–27 years) were studied to evaluate their baseline activity of cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, xanthine oxidase (XO) and N-acetyltransferase 2 (NAT2) based on the urinary metabolic indices of an 8-h urine sample collected after a 150-mg dose of caffeine and a 30-mg dose of dextromethorphan, and also the urinary excretion ratio of 6β-hydroxycortisol to cortisol. Thereafter, the subjects received 3.75 g of keishi-bukuryo-gan twice daily for seven days, and underwent the same tests on post-dose day 7. Key findings The geometric mean phenotypic index for CYP1A2 significantly decreased by 16% on day 7 compared with the baseline (P = 0.026). Keishi-bukuryo-gan did not alter the indices for CYP2D6, CYP3A, XO and NAT2. Conclusions Keishi-bukuryo-gan may inhibit the activity of CYP1A2, which is predominantly involved in oestrogen metabolism. However, TJ-25 is unlikely to participate in herb–drug interactions involving medications predominantly metabolized by CYP2D6, CYP3A, XO and NAT2.