肝移植后他克莫司的用量及血药浓度的变化规律

Relationship between oral doses of tacrolimus and changes in blood concentration after liver transplantation

目的 探讨肝移植后口服他克莫司 (FK5 0 6 )剂量与其全血浓度谷值的关系及浓度随时间而变化的规律。方法 回顾性分析肝移植后存活超过 1年、以FK5 0 6和糖皮质激素预防排斥反应的 2 0例患者的临床资料。结果 FK5 0 6初始口服剂量为 0 .15mg·kg-1·d-1时 ,术后第 1周内有5 3.4 %的血FK5 0 6浓度谷值高于理想治疗窗的 15 μg/L ,2 3.3%在 10～ 15 μg/L的理想范围内 ,2 3.3%低于 10 μg/L ;术后FK5 0 6的浓度 /剂量比值逐渐增高 ,第 2个月为高峰 (2 17.2± 136 .6 ) ,与第3、4、5、6、7、8和 11个月相比 ,差异有显著性 (P <0 .0 5 ) ,全组患者的浓度 /剂量比值总平均数为 190 .3±75 .4 ;维持术后第 1周内FK5 0 6浓度谷值在 10～ 15 μg/L的理想治疗范围内需要的剂量为(0 .10 137± 0 .0 2 6 10 )mg·kg-1·d-1,至 1年时维持浓度谷值为 5～ 7μg/L时需要的剂量为 (0 .0 6 4 6 6± 0 .0 2 797)mg·kg-1·d-1。结论 我国人肝移植后FK5 0 6口服剂量宜从 0 .1mg·kg-1·d-1左右开始 ,术后前 2个月内的血FK5 0 6浓度 /剂量比值高于其后各月的平均值。

Objective To investigate the relationship between dose and trough blood concentration of tacrolimus after orthotopic liver transplantation and the changes of time-dependent concentration. Methods The doses and trough blood concentrations of tacrolimus from 20 patients who survived longer than 1 year were summarized retrospectively.Results The initial oral doses of 0.15 mg·kg -1·d -1 as suggested by most surgeons led to 53.4 % of the measured whole blood concentrations in the first postoperative week were higher than 15 μg/L, 23.3 % of them within 10 μg/L to 15 μg/L and 23.3 % of them lower than 10 μg/L. The ratio of trough concentration/dose was increased gradually after transplantation and reached its peak at the second postoperative month, which was higher than those in the following month 3, 4, 5, 6, 7, 8 and 11 significantly (all P< 0.05). The average ratio of concentration/dose for 20 patients in one year of time was 190.3± 75.4. The dosage to maintain the required ideal treatment trough blood concentration from 10 μg/L to 15 μg/L in the first postoperative week was 0.101 37± 0.026 10 mg·kg -1·d -1. Following the decrease of the required treatment concentration, the ideal dosage was reduced to 0.064 66± 0.027 97 mg·kg -1·d -1 at the end of one year.Conclusion The tacrolimus should be given at a dose of about 0.1 mg·kg -1·d -1 initially after OLT under the current situation in China. The oral bioavailability of tacrolimus in liver transplantation recipients in China were higher than that reported by surgeons from other country. The ratio of concentration/dose in the second postoperative month was higher than the following month 3, 4, 5, 6, 7, 8 and 11.