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

发布时间：2018-03-07 13:26

本文选题：吗替麦考酚酯　切入点：麦考酚酸　出处：《中国临床药理学杂志》2015年02期 　论文类型：期刊论文

【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(P0.05);MPAG的体内暴露药量与肾功能存在明显负相关(P0.05),而MPA的体内暴露药量与患者肾功能无明显相关性(P0.05)。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。
[Abstract]:Objective to investigate the pharmacokinetics of the immunosuppressant motimefen (MMF) in patients with autoimmune diseases after initial administration and homeostasis. Methods 14 patients with autoimmune diseases were enrolled in this study. The serum concentrations of mycophenolate mofetil 0.75 g / q12 h were determined by high performance liquid chromatography (HPLC), the active metabolite of MMF and the secondary metabolite, phenolic glucose aldehydes malcophenolic acid (MPAG), were determined by high performance liquid chromatography (HPLC). Results the Cmax of MPA were 8.45 卤7.54 mg 路L -1 AUC0-12 h and 41.07 卤49.26 mg 路L -1 AUC0-12 h, respectively, and the Cmax of MPAG were 41.24 卤28.577.63 卤36.98 mg 路L -1 C 0-12 h and 41.07 卤49.26 mg 路L -1 mg 路L -1 Cmax after the first and steady state, respectively, which were 487.25 卤326.53 卤720.79 卤413.86 mg 路h 路L -1 for the first time and steady-state of MPA, respectively, and 41.24 卤28.577.63 卤36.98 mg 路L ~ (-1) mg 路L ~ (-1) Cmax for the first time and after steady-state for MPA were 487.25 卤326.53 卤720.79 卤413.86 mg 路h 路L ~ (-1) respectively. The differences of pharmacokinetic parameters were significant. Compared with the first administration of P0.05MPAG, there was a significant negative correlation between the dose of P0.05MPAG and the renal function, but there was no significant correlation between the exposure dose of MPA and the renal function of the patients. Conclusion there is no significant correlation between the exposure dose of MPA and the renal function of patients with autoimmune diseases (P 0.05). There were significant differences in plasma drug concentration and pharmacokinetics between the two groups. And there is obvious accumulation in the body.
【作者单位】：同济大学附属杨浦医院临床药学与药理学研究室;同济大学附属杨浦医院肾内科;
【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)
【分类号】：R969.1

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