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1.
J Pharm Pharmacol ; 64(5): 670-6, 2012 May.
Article in English | MEDLINE | ID: mdl-22471362

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 6ß-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


Subject(s)
Caffeine/metabolism , Cytochrome P-450 CYP1A2 Inhibitors , Dextromethorphan/metabolism , Drugs, Chinese Herbal/pharmacology , Herb-Drug Interactions , Hydrocortisone/metabolism , Acetyltransferases/metabolism , Adult , Caffeine/urine , Cytochrome P-450 CYP2D6/metabolism , Cytochrome P-450 CYP3A/metabolism , Dextromethorphan/urine , Drugs, Chinese Herbal/therapeutic use , Estrogens/metabolism , Female , Humans , Hydrocortisone/urine , Menopause , Phenotype , Phytotherapy/adverse effects , Reference Values , Xanthine Oxidase/metabolism , Young Adult
2.
Eur J Clin Pharmacol ; 63(4): 345-53, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17297618

ABSTRACT

OBJECTIVE: Shoseiryuto (TJ-19) contains eight herbal components, including Ephedra sinica, and has been used for treating asthma and allergic rhinitis in Asian countries for several centuries. In this study, we investigated the potential herb-drug interaction of TJ-19 in healthy volunteers and attempted to ascertain whether or not the interaction might be affected by the cytochrome P450 (CYP) 2D6 genotype. METHODS: We assessed the effect of TJ-19 on the activities of CYP1A2, CYP2D6, CYP3A, xanthine oxidase (XO), and N-acetyltransferase 2 (NAT2) in 37 healthy subjects. The subject pool consisted of 19 extensive metabolizers (EMs) with CYP2D6*Wild/*Wild, and 18 intermediate metabolizers (IMs) with CYP2D6*10/*10. The baseline activities of five enzymes were ascertained by their respective urinary metabolic ratios from an 8-h urine sample, after an oral 150-mg and 30-mg dose of caffeine and dextromethorphan were administrated, respectively. Thereafter, the subjects received 4.5 g of TJ-19 twice daily for 7 days, and underwent the same phenotyping test on postdose day 7. RESULTS: The activities of all enzymes examined did not differ before or after the 7-day administration of TJ-19. Consequently, the influence of the CYP2D6 genotype on the herb-drug interaction remained unsolved. CONCLUSION: Our results indicate that TJ-19 at the generally recommended dosage is unlikely to cause pharmacokinetic interaction with co-administered medications primarily dependent on the CYP1A2, CYP2D6, CYP3A, XO, and NAT2 pathways for elimination.


Subject(s)
Arylamine N-Acetyltransferase/metabolism , Cytochrome P-450 CYP2D6/drug effects , Drugs, Chinese Herbal/pharmacology , Herb-Drug Interactions , Xanthine Oxidase/metabolism , Adult , Arylamine N-Acetyltransferase/drug effects , Caffeine/pharmacology , Central Nervous System Stimulants/pharmacology , Cytochrome P-450 CYP2D6/genetics , Cytochrome P-450 CYP2D6/metabolism , Cytochrome P-450 CYP3A/drug effects , Cytochrome P-450 CYP3A/metabolism , Female , Humans , Male , Xanthine Oxidase/drug effects
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