CAJ | 학술논문

目的建立有限采样策略估算肾移植受者霉酚酸钠药-时曲线下面积(AUC)的公式.方法 2010-2013年南京军区福州总医院接受霉酚酸钠肠溶片(EC-MPS)联合钙调磷酸蛋白酶抑制剂(GNI)及泼尼松三联免疫抑制治疗的35例肾移植受者,血霉酚酸浓度采用均相酶免疫分析(EMIT)法测定,测定时间点为服药前及服药后0.5、1.0、1.5、2.0、3.0、4.0、6.0、8.0、12.0 h.采用WINNOLIN软件计算霉酚酸的药代动力学参数.多元逐步回归分析法得出适合中国人群服用不同CNI药物时的简化霉酚酸药-时AUC计算公式.结果 35例受者霉酚酸的AUC0～12h为14～ 67 mg·h/L,平均(37±14)mg·h/L;不同肾移植受者之间药代动力学参数个体差异大,霉酚酸的谷浓度(C0)与霉酚酸的AUC0～12h相关性差(r2 =0.090).服用他克莫司的受者采用4个时间点取样的霉酚酸浓度(C4、C6、C8、C12)得出霉酚酸的AUC简化计算公式为AUC =5.678+1.718×C4+2.853×C6+1.812×C8+3.413 ×C12;该公式的霉酚酸AUC预测值与AUC0-12h实测值相关性较好(r2=0.890,P＜0.05),绝对预测误差中位数为3.45％ (0.41％～24.71％),误差超过15％的比例为11.1％(2/18).服用环孢素A的患者采用4个时间点取样的霉酚酸浓度(C3、C4、C6、C8)得出霉酚酸AUC简化计算公式为AUC=7.072+1.525×C3+1.558×C4+1.573×C6+2.285×C8;该公式的霉酚酸AUC预测值与AUC0～12h实测值相关性好(r2 =0.952,P＜0.05),绝对预测误差中位数为6.50％ (0.02％～12.91％),误差超过15％的比例为0.上述两个公式经Bland-Altman分析,与霉酚酸AUC0～ 12h一致性良好.结论本研究拟合的4点霉酚酸AUC简化计算公式能较好地反映霉酚酸药-时AUC,适用于肾移植受者服用EC-MPS的治疗药物监测.
목적 건립유한채양책략고산신이식수자매분산납약-시곡선하면적(AUC)적공식.방법 2010-2013년남경군구복주총의원접수매분산납장용편(EC-MPS)연합개조린산단백매억제제(GNI)급발니송삼련면역억제치료적35례신이식수자,혈매분산농도채용균상매면역분석(EMIT)법측정,측정시간점위복약전급복약후0.5、1.0、1.5、2.0、3.0、4.0、6.0、8.0、12.0 h.채용WINNOLIN연건계산매분산적약대동역학삼수.다원축보회귀분석법득출괄합중국인군복용불동CNI약물시적간화매분산약-시AUC계산공식.결과 35례수자매분산적AUC0～12h위14～ 67 mg·h/L,평균(37±14)mg·h/L;불동신이식수자지간약대동역학삼수개체차이대,매분산적곡농도(C0)여매분산적AUC0～12h상관성차(r2 =0.090).복용타극막사적수자채용4개시간점취양적매분산농도(C4、C6、C8、C12)득출매분산적AUC간화계산공식위AUC =5.678+1.718×C4+2.853×C6+1.812×C8+3.413 ×C12;해공식적매분산AUC예측치여AUC0-12h실측치상관성교호(r2=0.890,P＜0.05),절대예측오차중위수위3.45％ (0.41％～24.71％),오차초과15％적비례위11.1％(2/18).복용배포소A적환자채용4개시간점취양적매분산농도(C3、C4、C6、C8)득출매분산AUC간화계산공식위AUC=7.072+1.525×C3+1.558×C4+1.573×C6+2.285×C8;해공식적매분산AUC예측치여AUC0～12h실측치상관성호(r2 =0.952,P＜0.05),절대예측오차중위수위6.50％ (0.02％～12.91％),오차초과15％적비례위0.상술량개공식경Bland-Altman분석,여매분산AUC0～ 12h일치성량호.결론 본연구의합적4점매분산AUC간화계산공식능교호지반영매분산약-시AUC,괄용우신이식수자복용EC-MPS적치료약물감측.
Objective To establish a formula for estimating area under the concentration-versustime curve (AUC) of mycophenolate sodium in Chinese renal allograft recipients with a limited sampling model.Methods A total of 35 renal allograft recipients were recruited from 2010 to 2013 to receive entericcoated mycophenolate sodium (EC-MPS),calcineurin (CNI) and prednisone as immunosuppressive triple therapy.The serum concentration of mycophenolic acid (MPA) was assayed by enzyme multiplied immunoassay technique (EMIT) at pre-dose (C0),0.5 (C0.5),1.0 (C1),1.5 (C1.5),2.0 (C2),3.0 (C3),4.0 (C4),6.0 (C6),8.0 (C8) and 12.0 (C12) h post-dose respectively.Pharmacokinetic parameters of MPA (C0,C12,Cmax,Tmax,AUC0-12 h) were calculated by software WINNOLIN.Simplified formulae for estimation of MPA-AUC in tacrolimus (Tac) group or cyclosporin A (CsA) group were established by multiple stepwise regression analysis.Results There were variable MPA AUC0-12h levels between 14 and 67 mg· h/L (mean:37 ± 14).The MPA trough level (C0) had no correlations with MPA AUC0-12h(r2 =0.090).The simplified MPA AUC formula for Tac group was AUC =5.678 + 1.718 × C4 +2.853 × C6 + 1.812 × C8 +3.413 × C12 with four sampling points (C4,C6,C8,C12).Estimated AUC with the formula had correlations with AUC0-12 h (r2 =0.890).The mean absolute predict error (APE) was 3.45％ (0.41％-24.71％) and the proportion of APE above 15％ stood at 11.1％ (2/18).In CsA group,the simplified MPA AUC formula was AUC =7.072 + 1.525 × C3 + 1.558 × C4 + 1.573 × C6 + 2.285 × C8.The correlation was r2 =0.952,mean APE was 6.50％ (0.02％-12.91％) and proportion of APE above 15％ stood at 0.The above formulae were observed to have agreement with AUC0-12h by Bland-Altman analysis.Conclusion The simplified MPA AUC formulae with 4-point sampling provide an effective approach for estimating full MPA AUC0-12h in Chinese renal recipients on EC-MPS plus tacrolimus or cyclosporin A.