The effect of Shoseiryuto, a traditional Japanese medicine, on cytochrome P450s, N-acetyltransferase 2 and xanthine oxidase, in extensive or intermediate metabolizers of CYP2D6.
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.


CONCLUSIONS
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.
Nakao
Masashi
M
Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Oe-honmachi 5-1, Kumamoto, 862-0973, Japan.
Muramoto
Yousuke
Y
Hisadome
Motoko
M
Yamano
Naoko
N
Shoji
Mami
M
Fukushima
Yumi
Y
Saruwatari
Junji
J
Nakagawa
Kazuko
K
D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000187:drug effects / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D041743:Herb-Drug Interactions; D006801:Humans; D008297:Male; D014969:Xanthine Oxidase / Q000187:drug effects / Q000378:metabolism*
D000697:Central Nervous System Stimulants; D004365:Drugs, Chinese Herbal; C090832:sho-seiryu-to; D002110:Caffeine; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D014969:Xanthine Oxidase; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human