环孢素在天疱疮患者中的群体药代动力学研究

Population pharmacokinetic study of cyclosporine A in pemphigus and pemphigoid patients

目的建立中国天疱疮患者应用环孢素(Cs A)的群体药代动力学(PPK)模型。方法回顾性收集47例天疱疮患者的98个Cs A常规血药浓度监测数据。所有患者均采用口服给药途径。用非线性混合效应模型建立PPK模型,并考察年龄、体重、性别、总胆红素、血细胞比容、体表面积、诊断类型、白细胞、血小板计数、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、白蛋白、直接胆红素和肌酸酐清除率等协变量对Cs A药代动力学参数的影响。结果性别和白蛋白是对Cs A清除率影响较为显著的因素。GOF图和Bootstrap结果显示,模型稳定可靠。结论成功建立我院天疱疮患者口服Cs A的PPK模型,该模型可为临床合理使用Cs A提供参考依据。

Objective To establish a population pharmacokinetic（ PPK） model of cyclosporine A（ Cs A） in pemphigus and pemphigoid patients. Methods A total of 98 Cs A therapeutic drug monitoring data were collected form 47 inpatients of dermatology department. Oral administration was used during the treatment. The influences of covariate effects,including age,weight,gender,total bilirubin in serum,hematocrit,body surface area,diagnosis,white blood cell,platelets,low density lipoprotein cholesterol,high density lipoprotein cholesterol,albumin and direct bilirubin in serum on parameters of PPK were estimated by NONMEM method,and a population pharmacokinetic model was set up.Results The gender and albumin were significant factors for Cs A clearance. GOF diagram and Bootstrap results show that the model is stable and reliable. Conclusion The PPK model of Cs A was successfully established in our hospital. The model can provide reference for clinical use of CsA.