肝移植受者早期EC-MPS药代动力学的临床特点

Pharmacokinetic characteristics of entericcoated mycophenolate sodium in liver transplant recipients early after transplantation

目的:观察肝移植术后早期麦考酚钠肠溶片(enteric-coated mycophenolate sodium,ECMPS)药代动力学特点.方法:25例肝移植受者术后联合应用他克莫司Tacrolimus(FK506)和EC-MPS治疗.ECMPS口服剂量为720 mg,2次/d.术后7、21 d分别在服药前及服药后1、1.5、2、2.5、3、4、6、8和12 h取外周血,采用高效液相色谱法(high performance liquid chromalography,H P L C)测定血浆麦考酚酸(m yc o p h e n o l i c acid,MPA)浓度.WinNonlin软件计算MPA药时曲线下面积(area of concentration-time under the curve,AUC).同时测定FK506谷浓度(FK506-C0 h)及肝、肾功能和血细胞记数.结果:合并43套数据,MPA-AUC0-12 h平均为40.36(μg·h)/mL±17.20(μg·h)/mL,Cmax为16.66μg/mL±9.73μg/mL,Tmax为3.14 h±1.78 h.MPA-C0 h-C12 h与MPA-AUC0-12 h的相关性不显著(r2<0.75).MPA-AUC0-12 h与FK506-C0 h、血清白蛋白水平及肌酐清除率显著相关性(P>0.05).结论:肝移植后早期患者服用EC-MPS MPAAUC0-12 h个体间差异很大;单个时间点MPA浓度不能有效反映MPA-AUC0-12 h;FK506-C0 h、血清白蛋白水平及肌酐清除率不影响MPAAUC0-12 h.

AIM： To investigate the pharmacokinetics of enteric-coated mycophenolate sodium （EC-MPS） in liver transplant recipients early after transplantation. METHODS： Twenty-five liver transplant recipient received tacrolimus and EC-MPS （720 mg, twice daily）. Mycophenolic acid （MPA） concentrations were measured by high performance liquid chromalography （HPLC） before dosing （C0 h） and at 0.5 h （C 0.5 h）, 1 h （C1 h）, 1.5 h （C1.5 h）, 2 h （C2 h）, 4 h （C4 h）, 6 h （C6 h）, 8 h （C8 h）, 10 h （C10 h）, and 12 h （C12 h） after dosing between days 7 and 21 postoperatively. Meanwhile, trough concentration （C0 h） of FK506, hepatic and renal function and blood cell counts were also measured. The WinNonlin software was used to calculate the area of concentration-time under the curve （AUC）. RESULTS： The average MPA-AUC0-12h was 40.36 （μg？h）/mL ± 17.20 （μg？h）/mL. The Cmax was 17.037 mg/L ± 7.632 mg/L, and the Tmax was 3.06 h ± 1.50 h. Individual concentrations of MPA-C0 h-C12 h were not significantly related with MPA-AUC0-12 h （r2 〈 0.75）. FK506-C0 h, serum albumin level and Cr-CL were not significantly correlated with MPA-AUC0-12 h （all P 〉 0.05）. CONCLUSION： The variability of MPA-AUC0-12 h is significant in liver transplant recipients early after transplantation. Single time-point MPA concentration can not reflect MPA-AUC0-12 h effectively. MPA-AUC0-12 h is less influenced by FK506 concentration, serum albumin and creatinine clearance.