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

J Pharm Pharmacol. 2012 May;64(5):670-6. doi: 10.1111/j.2042-7158.2011.01443.x. Epub 2012 Feb 7.

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 3.75g 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. K

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / metabolism
  • Adult
  • Caffeine / metabolism*
  • Caffeine / urine
  • Cytochrome P-450 CYP1A2 Inhibitors*
  • Cytochrome P-450 CYP2D6 / metabolism
  • Cytochrome P-450 CYP3A / metabolism
  • Dextromethorphan / metabolism*
  • Dextromethorphan / urine
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Estrogens / metabolism
  • Female
  • Herb-Drug Interactions*
  • Humans
  • Hydrocortisone / metabolism*
  • Hydrocortisone / urine
  • Menopause
  • Phenotype
  • Phytotherapy / adverse effects
  • Reference Values
  • Xanthine Oxidase / metabolism
  • Young Adult

Substances

  • Cytochrome P-450 CYP1A2 Inhibitors
  • Drugs, Chinese Herbal
  • Estrogens
  • keishibukuryogan
  • Caffeine
  • Dextromethorphan
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 CYP3A
  • Xanthine Oxidase
  • Acetyltransferases
  • Hydrocortisone