伏立康唑在肾移植患者中的群体药动学研究

目的：建立肾移植患者服用伏立康唑的群体药动学（PopPK）特征，探究影响伏立康唑药动学参数的因素，为临床个体化给药提供依据。方法：回顾性收集84例肾移植患者进行治疗药物监测的谷浓度和生理病理资料，利用Phoenix NLME软件建模，并用VPC法和Bootstrap法进行内部验证。结果：肾移植患者的伏立康唑的药动学特征符合一级消除一室模型，最终PopPK模型为：表观分布容积V（L）=183.69×1+（HGB-98）×0.016]×exp（η_V），清除率CL（L·h^-1）=7.24×1+（ALB-36）×0.037]×exp（η_CL）。结论：血红蛋白（HGB）对V有显著影响，白蛋白（ALB）对CL有显著影响，所建PopPK模型较稳定，可以较好地描述肾移植患者伏立康唑的药动学特征。

Population pharmacokinetics of voriconazole in renal transplant patients

OBJECTIVE To establish a population pharmacokinetic (PopPK) model of voriconazole in renal transplant patients, explore the potential factors effecting pharmacokinetic parameters of voriconazole, and provide a basis for clinical individualized therapy. METHODS Trough concentration and information were retrospectively collected for physiology and pathology of 84 renal transplant patients through routine TDM. Phoenix NLME software was used to establish a PopPK model. The final model was internally validated by VPC and Bootstrap methods. RESULTS A one-compartment model with first-order elimination was established with pharmacokinetic characteristics of voriconazole in renal transplant patients. The final PopPK model:apparent volume of distribution V(L)=183.69×1+(HGB-98)×0.016]×exp(η_V),clearance CL (L·h^-1)=7.24×1+(ALB-36)×0.037]×exp (η_CL). CONCLUSION V is significantly affected by hemoglobin (HGB) and CL is affected by albumin (ALB). The established PopPK model can adequately describe the pharmacokinetic characteristics of voriconazole in renal transplant patients.