Spina E, Arena D, Scordo M G, Fazio A, Pisani F, Perucca E
Institute of Pharmacology, University of Messina, Italy.
Ther Drug Monit. 1997 Oct;19(5):535-8. doi: 10.1097/00007691-199710000-00009.
The effect of ketoconazole (200 mg/d orally for 10 days) on the plasma concentrations of carbamazepine (CBZ) and its active metabolite carbamazepine-10,11-epoxide (CBZ-E) was assessed in eight patients with epilepsy stabilized on CBZ therapy. Administration of ketoconazole was associated with a significant increase in plasma CBZ concentrations (from 5.6 +/- 1.9 to 7.2 +/- 2.9 micrograms/ml on day 10 [means +/- SD, P < 0.02]), whereas plasma concentrations of CBZ-E were unchanged. After ketoconazole was discontinued, plasma CBZ levels decreased to pretreatment values. This interaction was probably mediated by an inhibiting action of ketoconazole on cytochrome CYP3A4, the main enzyme responsible for CBZ metabolism.
在8例接受卡马西平（CBZ）稳定治疗的癫痫患者中，评估了酮康唑（每日口服200mg，共10天）对卡马西平（CBZ）及其活性代谢产物卡马西平-10,11-环氧化物（CBZ-E）血浆浓度的影响。给予酮康唑后，血浆CBZ浓度显著升高（第10天时从5.6±1.9微克/毫升升至7.2±2.9微克/毫升[均值±标准差，P<0.02]），而CBZ-E的血浆浓度未发生变化。停用酮康唑后，血浆CBZ水平降至治疗前值。这种相互作用可能是由酮康唑对细胞色素CYP3A4的抑制作用介导的，CYP3A4是负责CBZ代谢的主要酶。
