合用他克莫司或环孢素对霉酚酸酯及其代谢产物药动学的影响

Pharmacokinetics of mycophenolate mofetil and its metabolisms when combined with tacrolimus or cyclosporine

目的比较合用他克莫司（FK506）与合用环孢素（Cs A）时霉酚酸酯（MMF）及其代谢产物的药动学差异。方法 20例服用MMF肾移植患者分为2组,分别为合用FK506组或合用Cs A组,于服药前和服药后共11个时间点采取外周静脉血,采用高效液相色谱法测定血浆中MMF及其代谢产物霉酚酸葡萄糖苷（MPAG）和霉酚酸酰基葡萄糖苷（Ac MPAG）浓度,计算药动学参数并进行比较。结果与FK506组相比,Cs A组霉酚酸（MPA）C0较低（1.58 vs 3.40 ng·mL^-1）,且代谢产物Ac MPAG的C0、Cmax和AUC0-12 h也显著低于FK506组（C0 0.20 vs 0.45 ng·mL^-1,Cmax 0.41 vs 0.72 ng·mL^-1,AUC0-12 h 3.04 vs 6.50ng·h·mL^-1）,2组间MPAG药动学参数差异无统计学意义。结论合用其他免疫抑制剂可能会对MMF及其代谢产物Ac MPAG的药动学产生显著影响。

Objective To compare the pharmacokinetics of mycophenolate mofetil（MMF） and its metabolisms when coadministrated with tacrolimus（FK506） or cyclosporine（Cs A）. Methods Totally of 20 recipients of aprimary cadaver kidney graft were divided into 2 groups： one combined with FK506 and the other with Cs A. Eleven samples were collected immediately before and after the morning dose of MMF. Plasma mycophenolic acid（MPA）, mycophenolic acid glucuronide（MPAG） and mycophenolic acid acyl glucuronide（Ac MPAG） levels w ere determined by high-performance liquid chromatography. Results The C0 of MPA in the Cs A group was lower than that in the FK506 group（1.58 vs 3.40 ng·mL^-1）. The C0, Cmax, AUC0 - 12 h of Ac MPAG in the Cs A group was also lower than that in the FK506 group（C00.20 vs 0.45 ng·mL^-1, Cmax 0.41 vs 0.72 ng·mL^-1, AUC0 - 12 h 3.04 vs 6.50 ng·h·mL^-1）. There was no difference between the 2 groups in pharmacokinetcs of MPAG. Conclusion The pharmacokinetics of mycophenolate mofetil and its metabolisms may be affected when co-administrated with other immunosuppressive drugs.