肝移植受者早期霉酚酸药代动力学临床特点

Clinical pharmacokinetics of mycophenolic acid of recipients in the early period of orthotopic liver transplantation

目的:探讨联合应用他克莫司(FK506)治疗肝移植受者早期霉酚酸(MPA)药代动力学的临床特点。方法:71例肝移植受者术后联合应用FK506和霉酚酸酯(MMF)治疗,MMF单剂口服剂量为1.0g,每日2次。患者术后1至2周内,分别在服药前及服药后0.5、1、1.5、2、4、6、8、10和12h取外周血,采用高效液相色谱法(HPLC)测定其血浆MPA浓度,分别标为MPA-C0～12h,并计算其曲线下面积(AUC)。同一天测定FK506谷浓度(FK506-C0h)及肝、肾功能和血细胞计数。结果:合并108套数据,MPA-AUC0～12h平均为(45.77±18.69)μg·h/ml(范围:10.66～117.01μg·h/ml)。MPA-C0～12h与MPA-AUC0～12h均相关(P<0.05),其中MPA-C2h的复相关系数最高(r2=0.424,P<0.05)。而FK506-C0h与MPA-AUC0～12h均无显著相关性(P>0.05)。血清白蛋白(ALB)异常者的MPA-AUC0～12h均显著低于ALB正常者(P<0.05)。结论:原位肝移植后患者个体间早期MPA-AUC0～12h差异很大;单个时间点MPA浓度不能有效反映其全程的血药浓度。FK506-C0h不影响MPA-AUC0～12h,而血清ALB浓度则对其有显著影响。

Objective To study the clinical characteristics of pharmacokinetic parameters of mycophenolic acid（MPA） in combination with Tacrolimus（FK506） in the early period of orthotopic liver transplantation.Methods Seventy-one liver transplant recipients received FK506 and mycophenolate mofetil（MMF） （1.0 g,twice daily） .MPA concentrations were measured by high performance liquid chromatography（HPLC） before dosing（C0h） and at 0.5 h（C0.5h） ,1 h（C1h） ,1.5 h（C1.5h） ,2 h（C2h） ,4 h（C4h） ,6 h（C6h） ,8 h（C8h） ,10 h（C10h） and 12 h（C12h） after dosing between day 7 and day 14 of post-operation.Trough concentration（C0h） of FK506,hepatic and renal function and blood cell counts were also measured at the same day.Results In the total 108 profiles of parameters,the average MPA-AUC0-12h was（45.77±18.69） μg·h/ml（range：10.66-117.01 μg·h/ml） .Every concentration of MPA-C0-12h was significantly related with MPA-AUC0-12h（P〈0.05） ,and the coefficient of determination of MPA-C2h was the highest（r2=0.424,P〈0.05） .FK506-C0h was not significantly correlated with MPA-AUC0-12h（P〉0.05） .The level of MPA-AUC0-12h in patients with abnormal serum albumin（ALB） level was less than that in patients with normal ALB level（P〈0.05） .Conclusions The variability of MPA-AUC0-12h was significant in the liver transplant recipients.Single time-point MPA concentration could not reflect MPA-AUC0-12h availably.MPA-AUC0-12h was influenced significantly by serum albumin level but not by the change of FK506-C0h.