FK506的药代动力学及其临床意义

Pharmacokinetics of oral FK506 in patients after renal transplantation

目的 测定肾移植患者的FK5 0 6药代动力学参数 ,阐明我国成人肾移植患者的药代动力学特点 ,以指导临床用药。 方法 对 13例肾移植术后患者给予FK5 0 6为基础的免疫抑制治疗 ,术后 2 4h开始服用FK5 0 6 ,剂量为 0 .10～ 0 .15mg·kg-1·d-1,分两次口服。首次服药后即刻 ,2 0、40、6 0、90min及 2、3、4、6、8、10h抽取血标本 ,采用MEIA法进行全血药物浓度测定 ,用 3P87软件计算有关药代动力学参数 ,并详细记录术后 1个月内的用药量。 结果 最大药物浓度 (Cmax)为(13.6 2 5 9± 4.1117)ng/ml,达峰值时间 [T(peak) ]为 (1.486 6± 1.0 72 5 )h ,分布相半衰期 (t1/ 2α)为(0 .7749± 0 .7791)h ,消除相半衰期 (t1/ 2 β)为 (10 .72 6 7± 10 .492 6 )h ,曲线下面积 (AUC)为 (91.0 415± 40 .76 94)ng·ml-1·h-1,清除率 (CL)为 (0 .0 0 46± 0 .0 0 36 )ng·ml-1·h-1,平均滞留时间 (MRT)为(8.15 40± 4.2 937)h。AUC与术后 1个月内FK5 0 6的用药量呈负相关 (相关系数r =- 0 .5 3,P =0 .0 38)。 结论 肾移植患者口服FK5 0 6的吸收速度很快 ,在 (1.5± 1.1)h内达高峰 ,平均半衰期为10 .7h ;药代动力学测定对临床用药具有指导意义。

Objective To carry out a pharmacokinetic evaluation of oral FK506 in 13 patients after renal transplant. Methods 13 patients after renal transplantation were given prograf based immunosupressive regimen 24 hours after surgery.Blood samples to determine FK506 levels were drawn in heparinized tube at 0、20、40、60、90 min and 2、3、6、8、10 hours after the first oral dosing.The whole blood concentrations were measured by MEIA and the pharmacokinetic parameters were calculated by 3P87 program.The FK506 doses were recorded in detail for the first month. Results Cmax was (13.6259±4.1117)ng/ml;T(peak) was (1.4866±1.0725)h;t1/2 α was (0.7749±0.7791)h,t1/2 β was (10.7267±10.4926)h;AUC was (91.0415±40.7694)ng·ml -1 ·h -1 ,CL was (0.046±0.0036)ng·ml -1 ·h -1 and MRT was (8.1540±4.2937)h.AUC was negative correlateld with prograf dose in the first month posttransplant (r=-0.53, P =0.038). Conclusions The absorption of oral administration of FK506 was rapid in patients after renal transplantation,and can achieve Cmax in (1.5±1.1)h,the mean half life time being 10.7 h.The pharmacokinetic parameters can be the guideline for FK506 application.