Townamchai N, Chancharoenthana W, Vadcharavivad S, Chariyavilaskul P, Pongpirul K, Leelahavanichkul A, Watanatorn S, Avihingsanon Y, Praditpornsilpa K, Srisawat N
Division of Nephrology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Division of Nephrology, Department of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Transplant Proc. 2015 Oct;47(8):2433-8. doi: 10.1016/j.transproceed.2015.08.013.
Tacrolimus pharmacokinetics prediction by CYP3A5 genotyping is not available in many Asian resource-limited settings. Therefore, an alternative technique is needed to estimate the dose of tacrolimus perioperatively. The 12-hour level after the first dose (C12-0) is an alternative technique for estimating the dose of tacrolimus. This simple and inexpensive calculation technique can be used by any transplantation center.
A prospective study on a cohort of 57 incident post-kidney transplant recipients was conducted. The whole-blood tacrolimus trough level (C12-0) was measured at 12 hours after the first dose (0.1 mg/kg) of orally administered tacrolimus during transplantation. Concomitant medications with CYP3A5 inhibitors/inducers were not allowed. Genotyping for CYP3A5 expression was carried out by reverse transcription polymerase chain reaction. The dosages and trough levels of tacrolimus at postoperative day 7 and postoperative months 1 to 3 were measured and analyzed for the dose requirements for therapeutic levels (mg/kg/d).
The doses of tacrolimus were widely diverse, ranging from 0.049 to 0.260 mg/kg/d and 0.031 to 0.298 mg/kg/d at day 7 and months 1 to 3, respectively. There were 9, 28, and 20 patients (15.8%, 49.1%, and 35.1%) with CYP3A5 *1/*1, *1/*3, and *3/*3, respectively. The CYP3A5 genotypes were significantly correlated with the target tacrolimus dose at day 7 (r(2) = 0.307) and the stable dose at months 1 to 3 (r(2) = 0.337). The C12-0 level also was significantly correlated with the dose of tacrolimus at day 7 (r(2) = 0.546) and the stable dose at months 1 to 3 (r(2) = 0.406).
There were strong correlations between the C12-0 level and the tacrolimus doses during the perioperative period at day 7 and the stable period at 1 to 3 months. Countries with limited resources for genotype testing can use the C12-0 level as an alternative to estimate the tacrolimus dose.
在许多亚洲资源有限的地区，通过CYP3A5基因分型预测他克莫司的药代动力学尚不可行。因此，需要一种替代技术来估计围手术期他克莫司的剂量。首剂后12小时的血药浓度（C12-0）是估计他克莫司剂量的一种替代技术。这种简单且成本低廉的计算技术可供任何移植中心使用。
对57例初次接受肾移植的受者进行了一项前瞻性研究。在移植期间口服首剂他克莫司（0.1mg/kg）后12小时测量全血他克莫司谷浓度（C12-0）。不允许使用CYP3A5抑制剂/诱导剂的联合用药。通过逆转录聚合酶链反应进行CYP3A5表达的基因分型。测量并分析术后第7天以及术后1至3个月他克莫司的剂量和谷浓度，以确定达到治疗浓度所需的剂量（mg/kg/d）。
他克莫司的剂量差异很大，术后第7天和术后1至3个月的剂量范围分别为0.049至0.260mg/kg/d和0.031至0.298mg/kg/d。分别有9例、28例和20例患者（15.8%、49.1%和35.1%）的CYP3A5基因型为*1/*1、*1/3和3/*3。CYP3A5基因型与术后第7天的他克莫司目标剂量（r(2)=0.307）以及术后1至3个月的稳定剂量（r(2)=0.337）显著相关。C12-0水平也与术后第7天的他克莫司剂量（r(2)=0.546）以及术后1至3个月的稳定剂量（r(2)=0.406）显著相关。
在围手术期第7天和术后1至3个月的稳定期，C12-0水平与他克莫司剂量之间存在很强的相关性。基因检测资源有限的国家可以使用C12-0水平作为估计他克莫司剂量的替代方法。
