吗替麦考酚酯在自身免疫性疾病患者体内的药代动力学研究  

Pharmacokinetics of mycophenolate mofetil in adult Chinese patients with autoimmune disease

作　　者：陈红君[1] 余自成[1] 周蓉[2] 沈杰[2] 干志彬[1] 唐原君[1] 

机构地区：[1]同济大学附属杨浦医院临床药学与药理学研究室,上海200090 [2]同济大学附属杨浦医院肾内科,上海200090

出　　处：《中国临床药理学杂志》2015年第2期102-105,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81302741);上海市卫生局科研基金资助项目(2009219);同济大学附属杨浦医院"晨光计划"基金资助项目(Ye1201220)

摘　　要：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。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 ±＆nbsp;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 （ P0.05 ）.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.

关 键 词：吗替麦考酚酯 麦考酚酸 酚化葡萄糖醛麦考酚酸 自身免疫性疾病 药代动力学 

分 类 号：R969.1[医药卫生—药理学] R979.5[医药卫生—药学]