伏立康唑与血液病患者常用药的药物相互作用研究

目的探讨伏立康唑与血液病患者常用药间的药物相互作用,指导伏立康唑个体化用药。方法收集2015-2017年天津市第一中心医院应用伏立康唑预防或治疗侵袭性真菌感染的血液病患者的血药浓度资料,应用非线性混合效应模型法,考察血液病患者常用药物与伏立康唑联用时的相互作用。结果伏立康唑清除率和表观分布容积的群体典型值分别为8.24 L·h^-1和163 L。群体药动学模型显示碱性磷酸酶对伏立康唑的清除率有显著影响(P<0.005)。联用兰索拉唑或环孢素时,伏立康唑的清除率分别降低33.4%、32.8%,而联用地塞米松使伏立康唑的清除率增加41.0%。结论临床上伏立康唑与兰索拉唑、环孢素或地塞米松联用时,需注意相互作用的产生,并合理调整用药剂量。

Study on drug interactions between voriconazole and commonly used clinical drugs in patients with hematologic diseases

AIM To explore the drug-drug interactions between voriconazole and commonly used clinical drugs in patients with hematological diseases,so as to give some suggestions about medication for the clinic.METHODS Blood concentration data of patients with hematological diseases in application of voriconazole to prevent or treat invasive fungal infections(IFI)in Tianjin First Central Hospital from 2015 to 2017 were collected.Population pharmacokinetics(PPK)model of voriconazole was developed by a nonliner mixed effect model(NONMEM)method to study the interactions of voriconazole with commonly used clinical drugs in patients with hematology.RESULTS The apparent clearance(CL)and apparent volume of distribution of voriconazole were 8.24 L·h^-1 and 163 L,respectively.The alkaline phosphatase showed a significant impact on CL of voriconazole(P<0.005)in population pharmacokingtic model.When coadministrated with lansoprazole or cyclosporine,the CL of voriconazole was decreased by 33.4% and 32.8%,respectively.However,dexamethasone increased the CL of voriconazole by 41.0%.CONCLUSION When voriconazole is combined with lansoprazole,cyclosporine or dexamethasone,the drug-drug interactions should be paid attention to and the dosage should be adjusted reasonably.