摘要
目的 研究成人肾移植激素撤除后麦考酚酸钠肠溶片的药代动力学特点,建立配伍他克莫司的血麦考酚酸浓度曲线下面积的有限检样方法.方法 30例成人肾移植受者,采用麦考酚酸钠肠溶片（EC-MPS）联合他克莫司的二联免疫抑制方案.血麦考酚酸浓度通过高效液相色谱法测定,采血点为服药前（C0）及服药后1、2.5、4、5、6、7、8、9、10.5、12 h,用梯形面积法计算浓度曲线下面积（AUC）,采用多元线性回归分析,确定相关采血点,确定有限取样方案.结果 通过多元线性回归分析出四点法估算的公式MPA-AUC=15.889＋0.692·C25＋1.071·C4＋4.948·C7＋4.477·C12（r2 =0.878）.采用Bland＆Altman分析法评估,四点法未超出置信限范围,与全点AUC有较好的一致性.模型绝对预测误差百分比（APE％）为（11.8±10.2）％,为临床可接受范围.结论该有限检样方案适用于监测激素撤除成人肾移植受者配伍他克莫司时血麦考酚酸浓度的曲线下面积.
Objective To investigate the pharmacokinetics of enteric-coated mycophenolate sodium in Chinese adult renal allograft recipients with steroids withdrawal and to generate the optimal model equations for estimation of the MPA area under the plasma concentration-time curve from 0 to 12 hours （AUC0-12 h） with a limited sampling strategy.Methods The pharmacokinetics in 30 Chinese renal allograft recipients treated with EC-MPS in comnbination with tacrolimus in the stable post transplant period were determined.MPA concentration was assayed by high performance liquid chromatography （HPLC） at pre-dose （C0） and 1（C1）,2.5 （C2.5）,4 （C4）,5（C5）,6 （C6）,7（C7）,8（C8）,9（C9）,10.5 （C10.5） and 12 （C12） hours after the morning dose of EC-MPS following an overnight fast.The model equations were generated by multiple stepwise regression analysis for estimation of the MPA-AUC.Results The best predictive equation model of systemic drug exposure was the following：MPA-AUC2.5 h-4 h-7 h-12 h =15.889 ＋0.692 · C2.5 ＋ 1.071 · C4 ＋4.948 ·C7 ＋4.477 · C12 （r2 =0.878）.The equation model showed an optimal agreement between the full AUCs and estimated AUCs by using Bland and Altman analysis.The mean absolute prediction error （APE％） for equation were 11.8％ ± 10.2％.Conclusions Limited sampling strategies are useful for MPA-AUC0-12 h monitoring in renal transplant recipients receiving EC-MPS.This predictive equation model provides an effective approach for estimation of full MPA-AUC0 12 h in Chinese adult renal allograft recipients treated with EC-MPS in combination with tacrolimus with steroids withdraw.
出处
《国际泌尿系统杂志》
2017年第5期751-755,共5页
International Journal of Urology and Nephrology
基金
深圳市科技计划项目（GCZX2015043016165448）
关键词
肾移植
激素类
药代动力学
Kidney Transplantation
Hormones
Pharmacokinetics
