CAJ | 학술논문

目的研究成人肾移植术后霉酚酸的药代动力学特点,建立配伍他克莫司的血霉酚酸浓度曲线下面积的有限检样方法.方法 42例成人肾移植受者,采用吗替麦考酚酯(MMF)联合他克莫司、泼尼松的三联免疫抑制方案.血霉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0.5、1、1.5、2、3、4、6、9和12h,用梯形面积法计算浓度曲线下面积,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得出3点估算MPA-AUC=7.297+2.819C1.5 h+3.297C4h+4.269C9 h[相关系数(r2)=0.878],4点估算的MPA- AUC=2.519+0.549C0.5 h+1.900C1.5 h+3.931C4h+4.037C9 h(r2=0.928).采用Bland & Altman分析法评估,3点法和4点法均未超出置信限范围,二者与全点AUG0-12h有较好的一致性.3点评估AUC与全点AUG0-12h差值为(11.7±8.32)mg·h·L-1,二者差值的95％置信区间为9.18～14.37 mg·h·L-1 (P＜0.01)；4点评估AUC与全点AUG0-12h差值为(1.65±7.98)mg·h·L-1,二者差值的95％置信区间为-0.84～4.13 mg·h·L-1 (P＜0.01).结论该有限检样方案适用于监测成人肾移植受者配伍他克莫司用药时血霉酚酸浓度的曲线下面积.
목적 연구성인신이식술후매분산적약대동역학특점,건립배오타극막사적혈매분산농도곡선하면적적유한검양방법.방법 42례성인신이식수자,채용마체맥고분지(MMF)연합타극막사、발니송적삼련면역억제방안.혈매분산농도통과고효액상색보법측정,채혈점위복약전(C0)급복약후0.5、1、1.5、2、3、4、6、9화12h,용제형면적법계산농도곡선하면적,채용다원선성회귀분석,학정상관채혈점,학정유한취양방안.결과 통과다원선성회귀분석득출3점고산MPA-AUC=7.297+2.819C1.5 h+3.297C4h+4.269C9 h[상관계수(r2)=0.878],4점고산적MPA- AUC=2.519+0.549C0.5 h+1.900C1.5 h+3.931C4h+4.037C9 h(r2=0.928).채용Bland & Altman분석법평고,3점법화4점법균미초출치신한범위,이자여전점AUG0-12h유교호적일치성.3점평고AUC여전점AUG0-12h차치위(11.7±8.32)mg·h·L-1,이자차치적95％치신구간위9.18～14.37 mg·h·L-1 (P＜0.01)；4점평고AUC여전점AUG0-12h차치위(1.65±7.98)mg·h·L-1,이자차치적95％치신구간위-0.84～4.13 mg·h·L-1 (P＜0.01).결론 해유한검양방안괄용우감측성인신이식수자배오타극막사용약시혈매분산농도적곡선하면적.
Objective To investigate the pharmacokinetics of mycophenolic acid (MPA) in Chinese adult renal allograft recipients,and to generate the validated model equations for estimation of the MPA area under the plasma concentration-time curve from 0 to 12 h (AUC0-12h) with a limitedsampling strategy.Methods The pharmacokinetics in 42 Chinese renal allograft recipients treated with mycophenolate mofetil in combination with tacrolimus and corticosteroids were determined. MPA concentration was assayed by high-performance liquid chromatography (HPLC) at pre-dose (G0) and at 0.5(G0.5h),1 (C1h),1.5 (C1.5h),2 (C2h),3(C3h),4 (C4h),6 (C6h),9 (C9h) and 12 (C12h) h,respectively.The modd equations were generated by multiple stepwise regression analysis for estimation of the MPA-AUC by a limited sampling strategy.Results The prediction formulas were as follows:MPA-AUC1.5 h-4h-9 h =7.297 + 2.819C1.5 h + 3.297C4 h + 4.269C9 h ( r2 =0.878) ; and MPA-AUG0.5 h-1.5 h-4 h-9 h =2.519 + 0.549G0.5 h + 1.900 C1.5 h + 3.931 C4 h + 4.037C9 h (r2 =0.928).We plotted the average of estimated AUC and full MPA-AUC0-12 h.The Bland 8 Altman analysis indicated good agreement to within 1.96SD.Mean difference of the prediction formula using the three time points of C1.5 h-C4 h-C9 h was (11.7 ± 8.32) mg·h·L-1 and 95％ confidence interval (CI) was (9.18～14.37) mg·h·L-1,p＜0.01 ; mean difference of the prediction formula using the four time points of G0.5 h-C1.5 h C4 h-C9 h was (1.65-±7.98) mg·h·L-1,and 95％ CI (-0.84～4.13) mg·h·L-1,P＜0.01.Conclusion This limited sampling strategy provides an effective approach for estimation of full MPA AUC0-12 h in Chinese adult renal allograft recipients treated with mycophenolate mofetil in combination with tacrolimus in the stable post transplant period.