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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(P>0.05);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)(P>0.05);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)(P>0.05)。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。
Objective: To investigate the pharmacokinetics of oral mycophenolate mofetil (MMF) and mycophenolate sodium enteric-coated tablets (EC-MPS) in early stage after renal transplantation, and provide a basis for clinical rational drug use. Methods: Twenty-six renal transplant recipients were divided into MMF group (n = 13) and EC-MPS group (n = 13) according to random number table. The two groups were given MMF (750 mg q12 h) or EC-MPS (720 mg q12 h), tacrolimus and methylprednisolone to prevent rejection. Venous blood samples (3 mL) were collected before morning medication and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h after the first day of operation. UPLC-UV analysis was used to determine mycophenolic acid MPA) plasma concentration. The pharmacokinetic analysis was performed with DAS 2.0 pharmacokinetics software. All dose-related pharmacokinetic parameters were dose-corrected (C max / D, C 0 / D, AUC 0-12 h / D And AUMC_ (0-12 h) / D). Statistical analysis was performed using SPSS 17.0 software. Results: The main pharmacokinetic parameters of MMF and EC-MPS on day 7 were (1.54 ± 0.9) h and (2.19 ± 1.56) h (P> 0.05), respectively; C max (5.12 ± 2.83) mg · L -1 · g -1 and 9.51 ± 7.38 mg · L -1 · g -1 (P> 0.05) 0-12 h) / D were (19.13 ± 7.78) mg · h · L -1 · g -1 and 25.96 ± 11.78 mg · h · L -1 · g -1, respectively (-1) (P> 0.05). Two groups of patients on drug-time curve were large differences between individuals, most patients observed double peak phenomenon, very few patients observed more peaks. In the MMF group and the EC-MPS group, the rates of MPA-AUC_ (0-12 h) low exposure group were 84.6% and 46.15%, respectively, and the target exposure group was 15.4% and 46.15% respectively. Only 1 EC-MPS group The patient is a high-exposure group. Conclusion: The pharmacokinetics of MMF and EC-MPS in patients with early renal transplantation vary widely. MPA-AUC_ (0-12 h) should be routinely monitored. At the same time, C_0 may be used as a reference to guide clinical adjustment of dosage. MPA-AUC_ (0-12 h) at routine doses of MMF and EC-MPS is low in patients with early renal transplantation, suggesting increased dosing.