肝移植患者中伏立康唑与他克莫司药物相互作用病例分析

Case Analysis of Drug Interaction of Voriconazole and Tacrolimus in Liver Transplant Patient

目的：对伏立康唑（voz）在两种不同的给药方式下（口服和静脉滴注）对他克莫司（TAC）药物浓度的影响程度进行比较，探讨两种药物相互作用机制。方法：观察分析l例服用TAC的肝移植术后随访患者，在应用VOZ治疗肺炎前后，TAC体内药物浓度的变化。结果：静脉滴注VOZ时TAC的平均谷浓度（c0）为18.6ng／ml（13.1～24ng／ml），c0／D为12.6ng／（ml·mg）[12～13.1ng／（ml·mg）]，口服VOZ与TAC联合用药时TAC的c0为7.2ng／ml（5.8～9.4ng／m1），c0／每日剂量（D）为18.5ng／（ml·mg）[15.6～24.8ng／（ml·mg）]。与联合用药前相比，静脉滴注VOZ使TAC的C0／D增加了641.2％，口服VOZ则使得TAC的c0／D增高了994.1％；口服VOZ联合应用时TAC的c0／D比静脉滴注voz联合应用时增加了47.6％。结论：肝移植术后患者在应用VOZ治疗肺炎后，TAC减少原剂量的1／3给药的方法并不适用，个体化给药很重要；二者相互作用的机制为：VOZ抑制肝脏和肠道中的CYP3A4／CYP3A5，使TAC的药物浓度显著升高；与VOZ静脉给药方式相比，口服VOZ联合用药时TAC具有较高的生物利用度。

OBJECTIVE： To compare the effects of voriconazole （VOZ） in two different modes of administration （oral and intravenous） on the concentration tacrolimus （TAC）, in order to investigate the mechanism of the interaction of the two drugs. METHODS： The concentrations of TAC in a patient after liver transplantation before and after taking VOZ. RESULTS： The median trough concentration （co） of TAC was 18.6 ng/ml （13.1-24 ng/ml）, median c0/D was 12.6 ng/（ml.mg）[12-13.1 ng/（ml·mg）] after intravenous infusion of VOZ; the median Co of TAC was 7.2 ng/ml （5.8-9.4 ng/ml）, median c0/D was 18.5 ng/（ml.mg）[15.6-24.8 ng/（ml. mg）] after oral dose of VOZ combined TAC. Compared with drug combination, c0/D of TAC increased by 641.2% after intravenous infusion of VOZ; that of TAC increased by 994.1% after oral administration of VOZ. c0/D of oral dose of VOZ combined with TAC was higher than that of intravenous infusion of VOZ by 47.6%. CONCLUSIONS： The patient after liver transplantation, points out the principles of TAC use： i.e. 1/3 decrease of the original dose isn＇t suitable to treat pneumonia, and highlight the importance of the individual administration. The mechanism of drug interaction has been also pointed out： i.e. VOZ inhibits CYP3A4/CYP3A5 enzymes in the liver and intestinal so as to increase the concentration of TAC significantly; compared with intravenous administration of VOZ, oral dose of VOZ combined with TAC has high bioavailability.