【摘要】 目的:研究肝移植受者环孢素A临床药动学特点,优化环孢素A治疗药物监测方案。方法:采用荧光偏振免疫法测定环孢素A血药浓度,计算临床药动学参数。建立AUC0-12h与浓度变量回归模型。对C0、C2常规监测数据进行分析。结果:环孢素代谢呈二房室开放模型。C0+C2与AUC0-12h相关较为强烈,C2与AUC0-4h和AUC0-12h的相关性高于C0。在估算AUC0→12h的回归模型中,C0+C2最好,SE和R-sq分别为501.0和94.7,其后是C6,C2,C9,C4和C0。结论:环孢素A临床药动学个体差异大。C0+C2两点监测是环孢素A最好的监测方法,可客观评价环孢素A体内药物暴露(AUC0-12h),减少急性排斥和药物中毒发生。C2/C0可以作为评价移植肝功能恢复的灵敏指标。更多还原

【Abstract】 OBJECTIVE To study clinical pharmacokinetics of cyclosporine A in liver transplant recipients and optimize cyclosporine A therapeutic drug monitoring strategy.METHODS The whole blood concentrations of cyclosporine A were measured by fluorescence polarization immunoassay（FPIA）,clinical pharmacokinetics parameters of cyclosporine A were computed.While blood cyclosporine A concentrations being independent variable,AUC₀-12h regression models were established.Routine monitoring data of C₀ and C₂ were analysed.RESULTS Cyclosporine A metabolizability were a linear two-compartment model with first-order absorption.There was strong correlation between C₀+C₂ and AUC₀-12h,and the correlation between C₂ and AUC₀-4h or AUC₀-12h was both more excellent than C₀.In regression models for calculating AUC₀-12h,C₀+C₂ single complex variable was the best,SE and R-sq were 501.02 and 94.7,respectively.Next was C₆,C₂,C₉,C₄,C₀.CONCLUSION Clinical pharmacokinetics of cyclosporine A was greatly different among patients.C₀+C₂ of two point monitoring was the best monitoring method for cyclosporine A.It can evaluate impersonally cyclosporine exposure（AUC₀-12h） in body and decrease rejection and drug toxicity.C₂/C₀ was a sensitive indication to evaluate function restoriation of the transplant liver.更多还原