Pithukpakorn Manop, Tiwawanwong Tiwat, Lalerd Yupaporn, Assawamakin Anunchai, Premasathian Nalinee, Tasanarong Adis, Thongnoppakhun Wanna, Vongwiwatana Attapong
Division of Medical Genetics, Mahidol University, Bangkok, Thailand.
Division of Nephrology, Department of Medicine, Mahidol University, Bangkok, Thailand.
Pharmgenomics Pers Med. 2014 Dec 5;7:379-85. doi: 10.2147/PGPM.S72760. eCollection 2014.
Despite use of a lower mycophenolate dose in Thai kidney transplant patients, acceptable graft and patient outcomes can be achieved. We therefore examined the pharmacokinetics of mycophenolic acid (MPA) by area under the curve (AUC) and investigated genetic contribution in mycophenolate metabolism in this population.
Kidney transplant recipients with stable graft function who were receiving mycophenolate mofetil 1,000 mg/d in combination with either cyclosporine or tacrolimus, and prednisolone were studied. The MPA concentration was measured by fluorescence polarization immunoassay (FPIA), at predose and 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after dosing. Genetic polymorphisms in UGT1A8, UGT1A9, and UGT2B7 were examined by denaturing high-performance liquid chromatography (DHPLC)-based single-base extension (SBE) analysis.
A total 138 patients were included in study. The mean AUC was 39.49 mg-h/L (28.39-89.58 mg-h/L), which was in the therapeutic range. The correlation between the predose MPA concentration and AUC was poor. The mean AUC in the tacrolimus group was higher than that in the cyclosporine group. Polymorphisms in UGT2B7 showed significant association with AUC.
Most of our patients with reduced mycophenolate dose had the AUC within the therapeutic range. Genetic polymorphisms in UGT2B7 may play a role in MPA metabolism in Thai kidney transplant patients.
尽管泰国肾移植患者使用的霉酚酸酯剂量较低，但仍可实现可接受的移植物和患者预后。因此，我们通过曲线下面积（AUC）研究了霉酚酸（MPA）的药代动力学，并调查了该人群中霉酚酸酯代谢的遗传因素。
对移植肾功能稳定、接受1000mg/d霉酚酸酯联合环孢素或他克莫司及泼尼松龙治疗的肾移植受者进行研究。通过荧光偏振免疫测定法（FPIA）在给药前及给药后1、1.5、2、4、6、8、10和12小时测量MPA浓度。通过基于变性高效液相色谱（DHPLC）的单碱基延伸（SBE）分析检测UGT1A8、UGT1A9和UGT2B7的基因多态性。
共有138例患者纳入研究。平均AUC为39.49mg·h/L（28.39 - 89.58mg·h/L），处于治疗范围内。给药前MPA浓度与AUC之间的相关性较差。他克莫司组的平均AUC高于环孢素组。UGT2B7基因多态性与AUC显著相关。
我们大多数使用较低剂量霉酚酸酯的患者AUC处于治疗范围内。UGT2B7基因多态性可能在泰国肾移植患者的MPA代谢中起作用。
