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

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.