In vitro inhibitory effects of Kampo medicines on metabolic reactions catalyzed by XXXX liver microsomes.

@entity1 @entity137 @entity5320 @entity58226 @entity5322 @entity5060 @entity4914
BACKGROUND: Although it is well known that drug-drug interactions may lead to @entity137 and therapeutic failure, little is known about the incidence and consequences of herb-drug interactions in @entity1 receiving Kampo medicines. METHODS: We evaluated the frequency of the combined use of Kampo medicines and Western drugs at Osaka University Hospital, and investigated the effects of these formulae on the metabolic activity of different cytochrome P450 (CYP) isoforms using pooled microsomes obtained from @entity1 liver. RESULTS: Twenty-two Kampo formulae were used together with 40 Western drugs catalyzed by the CYP isoforms @entity5322 , @entity5060 , @entity5320 and @entity4914 . Among the Kampo medicines, HOCHUEKKI-TO, SHOSAIKO-TO, NINJINYOUEI-TO, SAIREI-TO and KAKKON-TO were most frequently used during the study period (1996-2000). These were co-administered with 11 categories of drugs, which are substrates for @entity5322 . HOCHUEKKI-TO and SAIREI-TO were competitive inhibitors of @entity5322 with Ki values of 0.65 and 0.1 mg/mL, respectively. HOCHUEKKI-TO, SHOSAIKO-TO and @entity58226 inhibited the metabolic activities of @entity5060 , but had no effect on @entity5320 . HOCHUEKKI-TO and SAIREI-TO exhibited non-competitive inhibition of the metabolic activity of @entity5060 with a similar Ki value (0.7-0.8 mg/mL). SAIRE-TO (0.25 mg/mL) was a potent inhibitor of @entity4914 (inhibition > 68%). CONCLUSIONS: Frequently used Kampo medicines may interact with Western drugs, which are substrates for @entity5322 , @entity5060 and @entity4914 . Their co-administration should be undertaken with care.
