Pou L, Brunet M, Bilbao I, Andreu H, Andres I, Lopez R, Margarit C, Rimola A, Corbella J
Toxicology Service, Hospital Clínic, University of Barcelona, Spain.
Ther Drug Monit. 1998 Dec;20(6):602-6. doi: 10.1097/00007691-199812000-00003.
The aim of the Multicentric Liver Transplant Spanish Study was to evaluate tacrolimus therapy at the reduced, initial oral dose of 0.1 mg/kg per day to maintain the immunosuppressive potency of the drug and to avoid toxicity. The dosage of tacrolimus (D), the trough blood concentrations (C), and the evolution of the ratio (D/C) were followed up for 2 years after transplantation in 50 adult patients (38 men, 12 women) undergoing liver allograft transplantation. A total of 1732 samples were analyzed using the IMx tacrolimus method. The overall mean+/-SD concentrations were 10.84 ng/ml+/-5.32 ng/ml. During the first month, the median of the tacrolimus levels was 8.40 ng/ml, and 73.1% of the analyzed samples were within the established therapeutic range. The median oral tacrolimus dose was progressively reduced from 0.12 mg/kg per day during the first month to 0.058 mg/kg per day at the end of study period. A significant negative association was observed between the ratio of D/C and the post-transplantation period (r=-0.3624; p < 0.001). The median D/C ratio ranged from 0.0144 at the end of the first month to 0.0053 at 1 year. Significant declines in D/C were observed after the first and the third months after transplantation. The decrease in corticosteroid doses and the increase in serum albumin may explain the reduction in clearance with time.
西班牙多中心肝移植研究的目的是评估他克莫司初始口服剂量为每天0.1mg/kg时的治疗效果，以维持该药物的免疫抑制效力并避免毒性。对50例接受同种异体肝移植的成年患者（38例男性，12例女性）在移植后进行了2年的他克莫司剂量（D）、血药谷浓度（C）以及（D/C）比值变化的随访。使用IMx他克莫司检测方法共分析了1732份样本。总体平均±标准差浓度为10.84ng/ml±5.32ng/ml。在第一个月，他克莫司水平的中位数为8.40ng/ml，73.1%的分析样本在既定的治疗范围内。他克莫司口服剂量中位数从第一个月的每天0.12mg/kg逐渐降至研究期末的每天0.058mg/kg。观察到D/C比值与移植后时间之间存在显著的负相关（r = -0.3624；p < 0.001）。D/C比值中位数从第一个月末的0.0144降至1年时的0.0053。移植后第一个月和第三个月后观察到D/C显著下降。皮质类固醇剂量的减少和血清白蛋白的增加可能解释了清除率随时间的降低。
