The pharmacokinetics of mycophenolate mofetil in renal transplant recipients receiving standard-dose or low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus: the Symphony pharmacokinetic substudy
The pharmacokinetics of mycophenolate mofetil in renal transplant recipients receiving standard-dose or low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus: the Symphony pharmacokinetic substudy
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DOI：
10.1093/ndt/gfp162
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发表时间：
2009-07-01
影响因子：
6.1
通讯作者：
Brunet, Merce
中科院分区：
文献类型：
--
作者：
Grinyo, Josep M.;Ekberg, Henrik;Brunet, Merce
方法.进行了一项前瞻性、随机化、多中心、开放标签Symphony研究的3个月药代动力学子研究。83例成人肾移植患者接受标准剂量环孢素、MMF 2 g/天和皮质类固醇，或达克珠单抗诱导、MMF 2 g/天和皮质类固醇加低剂量环孢素、低剂量他克莫司或低剂量西罗莫司。比较治疗组间MPA及其代谢产物的浓度-时间曲线下面积（AUC（0-12））。在第7天、第1个月和第3个月，在MMF给药前和给药后20、40、75 min; 2、3、6、8、10和12 h进行药代动力学采样。与标准剂量环孢素相比，接受低剂量他克莫司或低剂量西罗莫司的患者在第7天和第1个月的MPA和第7天的游离MPA的AUC（0-12）值显著较高，而在第1个月的7-O-MPA-葡萄糖醛酸苷（MPAG）和第1和3个月的酰基-葡萄糖醛酸苷的AUC（0-12）值显著较低（P < 0.05）。第1个月时，他克莫司和西罗莫司组MPA和游离MPA的AUC（0-12）均显著高于环孢素组（P < 0.05）。三个低剂量组的MPA与MPAG暴露量之比均明显高于标准剂量环孢菌素组（P < 0.05）。结论。在给予相同剂量MMF的患者中，与低剂量他克莫司或低剂量西罗莫司相比，标准剂量和低剂量环孢素可降低MPA和游离MPA的暴露量。
Methods. A 3-month pharmacokinetic substudy of the prospective, randomized, multicentre, open-label Symphony study was performed. Eighty-three adult renal transplant patients received standard-dose cyclosporine, MMF 2 g/day and corticosteroids, or daclizumab induction, MMF 2 g/day and corticosteroids plus low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus. The area under the concentration-time curve (AUC(0-12)) of MPA and its metabolites between treatment groups was compared. Pharmacokinetic sampling was performed before MMF administration and at 20, 40, 75 min; 2, 3, 6, 8, 10 and 12 h post-dose on Day 7 and Months 1 and 3.Results. Compared with standard-dose cyclosporine, patients receiving low-dose tacrolimus or low-dose sirolimus had significantly higher AUC(0-12) values for MPA at Day 7 and Month 1 and for free MPA at Day 7, and significantly lower AUC(0-12) values for 7-O-MPA-glucuronide (MPAG) at Month 1 and for acyl-glucuronide at Months 1 and 3 (P < 0.05). AUC(0-12) of MPA and free MPA was significantly greater with low-dose tacrolimus and low-dose sirolimus than with low-dose cyclosporine in the first month (P < 0.05). The ratio of MPA to MPAG exposure was significantly higher in the three low-dose groups than in the standard-dose cyclosporine group (P < 0.05).Conclusions. Standard- and low-dose cyclosporine reduces the exposure of MPA and free MPA compared to low-dose tacrolimus or low-dose sirolimus in patients given the same dose of MMF.