吗替麦考酚酯在重症肌无力患者体内的药动学研究

A Pharmacokinetic Study of Mycophenolate Mofetil in Patients with Myasthenia Gravis

目的探讨吗替麦考酚酯在重症肌无力患者体内的药动学特征,评价ρ与AUC的相关性。方法选择8例年龄大于18岁,肝肾功能正常的重症肌无力患者,连续口服霉酚酸酯2 g·d^(-1)1周后,于再次给药前及给药后1,2,3,4,6,8,10 h取静脉血,用HPLC测定血浆药物浓度,用Win Nonlin程序统计分析。结果用非房室模型计算吗替麦考酚酯的药动学参数,主要的药动学参数为平均ρ_(max)为(11.39±3.23)μg·mL^(-1),t_(max)为(1.5±0.8)h,AUC_(0~12)为(38.71±11.23)μg·h·mL^(-1)。评价不同取血点的血药浓度与AUC的相关性,结果显示,ρ_2与AUC相关性最好(r^2=0.80);其次为ρ_0和ρ_4(r^2=0.75)。结论吗替麦考酚酯在重症肌无力患者体内的药动学个体差异大,但与健康受试者及器官移植患者无明显差别,考虑到临床取血的可行性,可将ρ_0作为该药常规血药浓度监测的指标。

OBJECTIVE To investigate the pharmacokinetics of mycophenolate mofetil in patients with myasthenia gravis,and evaluate the correlation between plasma concentration and AUC. METHODS Eight myasthenia gravis patients older than 18 years old with normal liver and renal function were included in this study. Blood samples were collected at 0,1,2,3,4,6,8,10 h after the patients were continuously given oral mycophenolate mofetil 2 g·d（-1）for one week. Plasma concentrations of mycophenolate mofetil were determined by HPLC method and data analysis was done by Win Nonlin program. RESULTS The main pharmacokinetic parameters of mycophenolate mofetil were as follows： ρ_（max）was（ 11. 39 ± 3. 23） μg · mL（-1）,t_（max）was（ 1. 5 ± 0. 8） h,AUC_（0-12h）was（ 38. 71 ± 11. 23） μg·h·mL（-1）. The ρ_2had the best correlation with AUC（ r-2= 0. 80） followed by ρ_0and ρ_4（ r-2= 0. 75）. CONCLUSION The pharmacokinetics of mycophenolate mofetil has great inter-individual differences,but without significant difference with those in healthy volunteers and transplant patients. The ρ_0can be used for routine therapeutic drug monitoring because of convenience and feasibility.