CAJ | 학술논문

目的：探讨免疫抑制剂吗替麦考酚酯（ MMF）在自身免疫性疾病患者体内首次给药和稳态后的药代动力学。方法自身免疫性疾病患者14例，口服吗替麦考酚酯0.75 g，q12 h，连续服药7 d达稳态，用高效液相色谱法测定MMF的活性代谢物麦考酚酸（ MPA）及二级代谢物酚化葡萄糖醛麦考酚酸（ MPAG）的血药浓度，并评价2种代谢物的体内暴露药量与患者肾功能的关系。结果 MPA首次服药及稳态后的Cmax分别为（8.45±7.54），（10.89±4.37）mg· L－1，AUC0－12h分别为（41.07±49.26），（55.09±41.74）mg· h· L－1；MPAG首次及稳态后的Cmax分别为（41.24±28.57），（67.63±36.98） mg · L－1， AUC0－12h分别为（487.25±326.53），（720.79±413.86）mg· h· L－1；两者在患者个体间药代动力学参数差异均较大，且稳态后的AUC0－12h与首次给药相比均明显增大（ P＜0.05）；MPAG的体内暴露药量与肾功能存在明显负相关（ P＜0.05），而MPA的体内暴露药量与患者肾功能无明显相关性（ P＞0.05）。结论自身免疫性疾病患者同方案给药后，MPA及MPAG血药浓度及药代动力学个体间差异大，且在体内存在明显蓄积现象。
목적：탐토면역억제제마체맥고분지（ MMF）재자신면역성질병환자체내수차급약화은태후적약대동역학。방법자신면역성질병환자14례，구복마체맥고분지0.75 g，q12 h，련속복약7 d체은태，용고효액상색보법측정MMF적활성대사물맥고분산（ MPA）급이급대사물분화포도당철맥고분산（ MPAG）적혈약농도，병평개2충대사물적체내폭로약량여환자신공능적관계。결과 MPA수차복약급은태후적Cmax분별위（8.45±7.54），（10.89±4.37）mg· L－1，AUC0－12h분별위（41.07±49.26），（55.09±41.74）mg· h· L－1；MPAG수차급은태후적Cmax분별위（41.24±28.57），（67.63±36.98） mg · L－1， AUC0－12h분별위（487.25±326.53），（720.79±413.86）mg· h· L－1；량자재환자개체간약대동역학삼수차이균교대，차은태후적AUC0－12h여수차급약상비균명현증대（ P＜0.05）；MPAG적체내폭로약량여신공능존재명현부상관（ P＜0.05），이MPA적체내폭로약량여환자신공능무명현상관성（ P＞0.05）。결론자신면역성질병환자동방안급약후，MPA급MPAG혈약농도급약대동역학개체간차이대，차재체내존재명현축적현상。
Objective To investigate the pharmacokinetics of mycophe-nolate mofetil ( MMF) in Chinese adult patients with autoimmune disea-ses.Methods Fourteen patients with autoimmune disease were included in this study.Oral dose ( MMF 0.75 g, q12 h) was given for the first time and 7 days later steady -state.Serum concentrations of the myco-phenolic acid ( MPA) , an active metabolite of the pro -drug MMF, and its phenol glucuronide metabolite ( MPAG ) were determined by HPLC method.Pharmacokinetic parameters of MPA and MPAG were calculated and influences of renal function on MPA drug exposure and MPAG drug exposure in steady -state were investigated.Results The main pharma-cokinetic parameters of MPA after first -dose and steady -state were as follows: Cmax were ( 8.45 ±7.54 ) , ( 10.89 ±4.37 ) mg · L-1 , AUC0-12 h were (41.07 ±49.26 ), (55.09 ±41.74 ) mg· h· L-1 and the main pharmacokinetic parameters of MPAG after first -dose and steady-state were as follows: Cmax were (41.24 ±28.57 ), (67.63 ± 36.98) mg · L-1, AUC0-12h were (487.25 ±326.53 ), (720.79 ± 413.86 ) mg· h· L-1.A large variability existed in pharmacokinetic parameters of MPA and MPAG.The differences in pharmacokinetic parameters are larger between individual patient of the two groups , the AUC0-12h of steady -state compared with the first administration were both obviously greater ( P<0.05 ).There was an obviously inverse relation-ship between MPAG drug exposure and renal function ( P<0.05 ) , however , MPA drug exposure was less affected by renal function ( P>0.05 ).Conclusion In patients with autoimmune disease receiving a fixed MMF dose , there is a large inter-individual variability of MMF pharmacokinetics and accumulation of MPA and MPAG drug exposure .In addition, a significant accumulated phenomenon was found.