肾移植患者中麦考酚酸及其葡萄糖苷酸代谢物的稳态药动学

Pharmacokinetics of total and free mycophenolic acid and its glucuronide metabolite in renal transplant recipients at steady state

目的探讨肾移植患者中麦考酚酸(MPA)及其葡萄糖苷酸代谢物(MPAG)的药动学特征。方法12名肾移植患者口服麦考酚酸酯0.75g bid。采集术后第7-10天12h内11个时间点的血浆样本。HPLC法测定血浆中游离和总的MPA和MPAG浓度。计算MPA和MPAG的游离分数和药动学参数。结果MPA和MPAG的游离分数分别为96.50%±2%和65.40%±8%。总的和游离的MPA稳态主要药动学参数分别为tmax均为(1.92±0.95)h;cmax分别为(9.35±3.35)mg/L,(0.54±0.48)mg/L;AUC0-12分别为(20.24±6.54)mg.h.L-1,(0.73±0.52)mg.h.L-1;MRT0-12分别为(3.22±0.90)h,(3.13±0.99)h。总的和游离的MPAG稳态药动学参数:tmax均为(3.33±1.72)h;cmax分别为(97.33±32.56)mg/L,(29.92±8.46)mg/L;AUC0-12分别为(656.40±148.20)mg.h.L-1,(222.10±58.08)mg.h.L-1;MRT0-12分别为(5.52±0.42)h,(5.44±0.46)h。结论MPA个体间药动学差异大,以监测其游离浓度为佳。

Purpose To investigate the pharmacokinetics （PK） characteristics of total and free mycophenolic acid （MPA） and its glucuronide metabolite （MPAG） in renal transplant recipients at steady state. Methods Plasma samples were collected from 12 renal transplant recipients administrated with MMF 0.75 g bid 7 - 10 days after transplantation. Total and free MPA and MPAG were determined by HPLC method. The unbound fraction of MPA and MPAG and their PK parameters were estimated. Results The unbound fraction of MPA and MPAG were 96.50 % ± 2 % and 65.40 % ± 8 % respectively. The PK parameters for total and free MPA at steady state were tmax（1. 92 ± 0. 95） h, cmax （9.35 ± 3.35） mg/L and （0.54 ± 0.48） mg/L, AUC0-12 （20.24 ± 6. 54） and （0.73 ± 0.52） mg · h · L^-1 ,MRT0-12 （3. 22 ± 0.90） h and （3.13 ± 0. 99） h respectively. Those of MPAG were tmax（3. 33 ± 1.72） h, cmax（97. 33 ± 32. 56） mg/L and （29. 92 ± 8. 46） mg/L,AUC0-12 （656. 40 ± 148. 20） and （222.10±58.08） mg·h· L^-1,MRT0-12（5.52±0.42） h and（5.45±0.46） hrespectively. Conclusions Inter-individual MPA PK characteristics were considerably variable and it may be better to monitor its free form concentration in clinical settings.