吗替麦考酚酯胶囊和麦考酚钠肠溶片在早期肾移植患者中的药动学

发布时间：2018-03-17 11:07

本文选题：吗替麦考酚酯　切入点：麦考酚钠肠溶片　出处：《中国医院药学杂志》2017年10期 　论文类型：期刊论文

【摘要】：目的:探讨肾移植术后早期患者口服吗替麦考酚酯胶囊(MMF)和麦考酚钠肠溶片(EC-MPS)的药动学特点,为临床合理用药提供依据。方法:选取26例肾移植患者,按随机数字表法分为MMF组(n=13)和EC-MPS组(n=13),两组患者分别于术后第1天给予MMF(750 mg q12 h)或EC-MPS(720 mg q12 h)、他克莫司、甲泼尼龙预防排斥反应。于术后第7天的早上服药前及服药后0.5,1,1.5,2,3,4,6,8,10,12 h采集静脉血样3 mL,采用UPLC-UV分析方法测定霉酚酸(MPA)血浆浓度。以DAS 2.0药动学软件进行药动学分析,所有与剂量相关的两组药动学参数分别进行了剂量校正(C_(max)/D,C_0/D,AUC_(0-12 h)/D及AUMC_(0-12 h)/D)。用SPSS 17.0软件进行统计学分析。结果:术后第7天MMF和EC-MPS的主要药动学参数t_(max)分别为(1.54±0.9)h和(2.19±1.56)h(P0.05);C_(max)/D分别为(5.12±2.83)mg·L~(-1)·g~(-1)和(9.51±7.38)mg·L~(-1)·g~(-1)(P0.05);AUC_(0-12 h)/D分别为(19.13±7.78)mg·h·L~(-1)·g~(-1)和(25.96±11.78)mg·h·L~(-1)·g~(-1)(P0.05)。两组患者的药-时曲线个体间差异均较大,大部分患者观察到有双峰现象,极个别患者观察到有多峰。MMF组和EC-MPS组患者的MPA-AUC_(0-12 h)低暴露组比例分别为84.6%和46.15%,目标暴露组比例分别为15.4%和46.15%,仅有1例EC-MPS组患者为高暴露组。结论:MMF和EC-MPS在早期肾移植患者体内的药动学个体差异较大,需要常规监测MPA-AUC_(0-12 h),同时可结合C_0作为参考,以指导临床调整用药剂量。MMF和EC-MPS常规剂量下的MPA-AUC_(0-12 h)在早期肾移植患者中偏低,建议增加给药剂量。
[Abstract]:Objective: to investigate the pharmacokinetic characteristics of Mutimefen capsule (MMF) and mycophenolic sodium enteric-coated tablets (EC-MPS) in early stage of renal transplantation, and to provide evidence for rational drug use in clinic. Methods: 26 patients with renal transplantation were selected. The patients in MMF group and EC-MPS group were given MMF(750 mg q12 h) or EC-MPS(720 mg Q12 h, tacrolimus on the first day after operation. Methylprednisolone was used to prevent rejection. Venous blood samples were collected for 3 mL at the morning of 7 days after operation and before and after taking the drug. The plasma concentration of mycophenolate mofetil was determined by UPLC-UV. The pharmacokinetic analysis was performed with DAS 2.0 pharmacokinetic software. All dose-related pharmacokinetic parameters of the two groups were dose-corrected respectively. The main pharmacokinetic parameters of MMF and EC-MPS on the 7th day after operation were 1.54 卤0.9h and 2.19 卤1.56hP0.05C / D, respectively. Statistical analysis was carried out using SPSS 17.0 software. Results: the main pharmacokinetic parameters of MMF and EC-MPS were 1.54 卤0.9h and 2.19 卤1.56hP0.05C / D, respectively. The results showed that the main pharmacokinetic parameters of MMF and EC-MPS were 1.54 卤0.9 h and 2.19 卤1.56 h / d respectively. And 9.51 卤7.38 渭 g 路L ~ (-1) 路g ~ (-1) 路g ~ (1)) 路P ~ (0.05) (P ~ (0.05) P = 19.13 卤7.78 mg 路h 路L ~ (-1) 路g ~ (-1)) and 25.96 卤11.78 ~ 11.78 mg 路L ~ (-1) 路g ~ (-1) 路g ~ (-1), respectively. Most of the patients observed a bimodal phenomenon. In very few patients, the proportions of MPA-AUC_(0-12 h in low exposure group were 84.6% and 46.15, those in target exposure group were 15.4% and 46.15, respectively. Only one patient in EC-MPS group was in high exposure group. Conclusion\% MMF and EC-MPS are in early stage of renal metastasis. The pharmacokinetics of the patients in vivo varies greatly. Routine monitoring of MPA-AUC_(0-12 hens is needed, and C0 can be used as a reference to guide the clinical adjustment of dosage. MMF and MPA-AUC_(0-12 h under the routine dose of EC-MPS) in early renal transplantation patients. It is suggested to increase the dosage of drugs.
【作者单位】：郑州大学第一附属医院药学部;
【基金】：河南省医学科技攻关计划项目(编号:201602037)
【分类号】：R969.1

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