Influence of UGT1A8 and UGT2B7 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients
Influence of UGT1A8 and UGT2B7 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients
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DOI：
10.1007/s00228-006-0248-2
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发表时间：
2007-03-01
影响因子：
2.9
通讯作者：
Suzuki, Toshio
中科院分区：
文献类型：
--
作者：
Kagaya, Hideaki;Inoue, Kazuyuki;Suzuki, Toshio
目的：UGT 1A 8和UGT 2B 7是霉酚酸（MPA）葡萄糖醛酸化的重要尿苷二磷酸-葡萄糖醛酸转移酶亚型。本研究的目的是阐明MPA的药代动力学在UGT 1A 8和UGT 2B 7基因型在日本肾移植recipients.Methods：72个收件人接受重复剂量的霉酚酸酯和他克莫司。在肾移植后第28天，使用高效液相色谱法测定接下来24小时的血浆MPA浓度。结果：UGT 1A 8和UGT 2B 7基因型间MPA日间和夜间药代动力学无显著性差异。UGT 1A 8 *1/*1、*1/*2和 *2/*2中MPA的平均日间剂量校正AUC（0-12）分别为2.47、2.33和2.57 ng中心点h/ml/mg/kg（P=0.7711），平均夜间AUC（0-12）分别为2.15、2.00和2.08 ng中心点h/ml/mg/kg（P=0.4656）。UGT 2B 7 *1/*1、*1/*2和 *2/*2中MPA的平均日间和夜间剂量校正AUC（0-12）分别为2.61、2.24和2.03 ng中心点h/ml/mg/kg和2.18、1.94和1.45 ng中心点h/ml/mg/kg（P=0.3475和0.2575）。平均夜间C-max，t（max），AUC（6-12）/AUC（0-12）比（肝肠循环和再循环比）MPA在所有UGT 1A 8和UGT 2B 7基因型分别较低，较长，较高，比白天value.Conclusions：UGT 1A 8和UGT 2B 7等位基因变异似乎不影响日本个体间变异的血浆MPA浓度。无论UGT 1A 8和UGT 2B 7基因多态性如何，MPA通过肠肝再循环的吸收在夜间较高。
Objective: UGT1A8 and UGT2B7 are important uridine diphosphate-glucuronosyltransferase isoforms for the glucuronidation of mycophenolic acid (MPA). The aim of this investigation was to elucidate MPA pharmacokinetics in UGT1A8 and UGT2B7 genotypes in Japanese renal transplant recipients.Methods: Seventy-two recipients received repeated doses of mycophenolate mofetil and tacrolimus. On day 28 after renal transplantation, plasma MPA concentrations were measured for the next 24 h using high-performance liquid chromatography. UGT1A8*2 (A(173)G) and UGT2B7*2 (Y-268) were detected using a PCR-RFLP-based procedure.Results: There were no significant differences in daytime and nighttime pharmacokinetics of MPA between UGT1A8 or UGT2B7 genotypes. The mean daytime dose-adjusted AUC(0-12) of MPA in UGT1A8*1/*1, *1/*2 and *2/*2 were 2.47, 2.33 and 2.57 ng center dot h/ml/mg/kg (P=0.7711), and the mean nighttime AUC(0-12) were 2.15, 2.00 and 2.08 ng center dot h/ml/mg/kg (P=0.4656). The mean daytime and nighttime dose-adjusted AUC(0-12) of MPA in UGT2B7*1/*1, *1/*2 and *2/*2 were 2.61, 2.24 and 2.03 ng center dot h/ml/mg/kg and 2.18, 1.94, and 1.45 ng center dot h/ml/mg/kg, respectively (P=0.3475 and 0.2575). The mean nighttime C-max, t(max), and AUC(6-12)/AUC(0-12) ratio (enterohepatic circulation and recirculation ratio) of MPA in all UGT1A8 and UGT2B7 genotypes were lower, longer, and higher, respectively, than the daytime values.Conclusions: Both UGT1A8 and UGT2B7 allelic variants seem not to affect Japanese interindividual variability for plasma MPA concentration. Regardless of UGT1A8 and UGT2B7 genetic polymorphisms, the absorption of MPA through enterohepatic recirculation is higher at night.