De Meyer Martine, Haufroid Vincent, Kanaan Nada, Darius Tom, Buemi Antoine, De Pauw Luc, Eddour Djamila Chaïb, Wallemacq Pierre, Mourad Michel
Department of Surgery, Surgery & Abdominal Transplantation Division, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Department of Clinical Chemistry, Université catholique de Louvain, Cliniques universitaires Saint-Luc, Brussels, Belgium.
Pharmacogenomics. 2016 Jun;17(9):1019-27. doi: 10.2217/pgs-2016-0005. Epub 2016 Jun 8.
The once daily tacrolimus formulation (Tac-OD) has been associated with better patient adherence and low variability in exposure. Patients carrying the CYP3A5*1 allele show accelerated clearance of Tac. Authors prospectively evaluate a simplified strategy for Tac-OD administration.
PATIENTS & METHODS: After grafting, 151 patients were divided into four groups and received a daily dose calculated according to CYP3A5 genotypes and unchanged for the first 3 days: CYP3A5*3/3: 0.20 mg/kg/day, CYP3A53/3: 0.25 mg/kg/day, CYP3A51/3: 0.30 mg/kg/day and CYP3A51/*1: 0.35 mg/kg/day. The dose was adaptated on day 4 and remained unchanged a further three days and so on.
On day 3, median Cmin fell within the therapeutic range in all study groups. CYP3A5 expressors require significantly higher Tac-OD throughout the follow-up period to achieve a comparable Cmin.
This simplified strategy does not hamper treatment efficacy.
每日一次的他克莫司制剂（Tac-OD）与患者更好的依从性以及较低的血药浓度变异性相关。携带CYP3A5*1等位基因的患者他克莫司清除加快。作者前瞻性评估了一种简化的Tac-OD给药策略。
移植后，151例患者被分为四组，并根据CYP3A5基因型计算每日剂量，且在开始3天保持不变：CYP3A5*3/3：0.20mg/kg/天，CYP3A52/3：0.25mg/kg/天，CYP3A51/3：0.30mg/kg/天，CYP3A51/*1：0.35mg/kg/天。第4天调整剂量，并在接下来的3天保持不变，依此类推。
在第3天，所有研究组的Cmin中位数均落在治疗范围内。在整个随访期间，CYP3A5表达者需要显著更高剂量的Tac-OD才能达到可比的Cmin。
这种简化策略不会妨碍治疗效果。
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