Takahashi K, Uejima E, Morisaki T, Takahashi K, Kurokawa N, Azuma J
Department of Clinical Evaluation of Medicines and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
J Clin Pharm Ther. 2003 Aug;28(4):319-27. doi: 10.1046/j.1365-2710.2003.00500.x.
Although it is well known that drug-drug interactions may lead to toxicity and therapeutic failure, little is known about the incidence and consequences of herb-drug interactions in patients receiving Kampo medicines.
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 human liver.
Twenty-two Kampo formulae were used together with 40 Western drugs catalyzed by the CYP isoforms CYP3A4, CYP2C9, CYP2D6 and CYP1A2. 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 CYP3A4. HOCHUEKKI-TO and SAIREI-TO were competitive inhibitors of CYP3A4 with Ki values of 0.65 and 0.1 mg/mL, respectively. HOCHUEKKI-TO, SHOSAIKO-TO and SAIREI-TO inhibited the metabolic activities of CYP2C9, but had no effect on CYP2D6. HOCHUEKKI-TO and SAIREI-TO exhibited non-competitive inhibition of the metabolic activity of CYP2C9 with a similar Ki value (0.7-0.8 mg/mL). SAIRE-TO (0.25 mg/mL) was a potent inhibitor of CYP1A2 (inhibition > 68%).
Frequently used Kampo medicines may interact with Western drugs, which are substrates for CYP3A4, CYP2C9 and CYP1A2. Their co-administration should be undertaken with care.
尽管众所周知药物相互作用可能导致毒性和治疗失败，但对于接受汉方药治疗的患者中，草药与药物相互作用的发生率及后果却知之甚少。
我们评估了大阪大学医院汉方药与西药联合使用的频率，并使用从人肝脏获得的微粒体池研究了这些方剂对不同细胞色素P450（CYP）同工酶代谢活性的影响。
22种汉方方剂与由CYP同工酶CYP3A4、CYP2C9、CYP2D6和CYP1A2催化的40种西药联合使用。在研究期间（1996 - 2000年），汉方药中，补中益气汤、小柴胡汤、人参养荣汤、柴苓汤和葛根汤使用最为频繁。它们与11类作为CYP3A4底物的药物联合使用。补中益气汤和柴苓汤是CYP3A4的竞争性抑制剂，Ki值分别为0.65和0.1mg/mL。补中益气汤、小柴胡汤和柴苓汤抑制CYP2C9的代谢活性，但对CYP2D6无影响。补中益气汤和柴苓汤对CYP2C9的代谢活性表现出非竞争性抑制，Ki值相似（0.7 - 0.8mg/mL）。柴苓汤（0.25mg/mL）是CYP1A2的强效抑制剂（抑制率>68%）。
常用汉方药可能与作为CYP3A4、CYP2C9和CYP1A2底物的西药发生相互作用。它们的联合使用应谨慎进行。
