Pharmacokinetics of enteric-coated mycophenolate sodium in Chinese renal transplantation recipients

Background Mycophenolic acid （MPA） as an anti-proliferative immune-suppressive agent is used in the majority of immunosuppressive regimens in solid organ transplantation. This study aimed to investigate the pharmacokinetic （PK） characteristics of enteric-coated mycophenolate sodium （EC-MPS） and area under the curve （AUC） from 0 to 12 hours with limited sampling strategies （LSSs） in Chinese renal transplant recipients. Methods This study was conducted in 10 Chinese renal transplant patients receiving living donor and treated with EC-MPS, cyclosporine, and corticosteroids. MPA concentrations were measured by enzyme multiplied immunoassay technique （EMIT）. Whole 12-hour PK profiles were obtained on Day 4 after operation. LSSs with jackknife technique, multiple stepwise regression analysis, and Bland-Altman analysis were developed to estimate MPAAUC. Results The mean maximum plasma concentration, the mean time for it to reach peak （Tmax）, and the mean MPA AUC were （11.38±2.49） mg/L, （4.85±3.32） hours, and （63.19±13.54） mg.h.L1, respectively. Among the 10 profiles, MPA AUC of four patients was significantly higher than that of the other six patients, and the corresponding Tmax was significantly longer than that of the other six patients. No patient exhibited a second peak caused by enterohepatic recirculation. The best models were as follows： 27.46＋0.94C3＋3.24C8＋2.81C10 （f2=0.972）, which was used to predict AUC of fast metabolizer with a mean prediction error （MPE） of -0.21% and a mean absolute prediction error （MAE） of 2.59%; 36.65＋3.08Ce＋5.30C10-4.04C12 （r2=0.992）, which was used to predict AUC of slow metabolizer with a MPE of 0.58% and a MAE of 1.95%. Conclusions The PKs of EC-MPS had a high variability among Chinese renal transplant recipients. The preliminary PK data indicated the existence of slow and fast metabolizer. These findings may be associated with the enterohepatic rec.irculation.

Nonlinear relationship between enteric-coated mycophenolate sodium dose and mycophenolic acid exposure in Han kidney transplantation recipients

The aim of the research was to investigate the pharmacokinetics(PK) of enteric-coated mycophenolate sodium(EC-MPS) by quantification of the active metabolite of mycophenolic acid(MPA)after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from0 to 12 h after EC-MPS administration. MPA plasma concentrations were measured by UPLC–UV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to900 mg, C_(max) and AUC_(0–12h) did not increase with dose escalation. The AUC_(0–12h), C_(max), C_0 and T_(max) for the 540 720 and 900 mg doses were not significantly different, respectively(P 40.05). AUC_0–12 h and C_(max) were increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC_(0–12h), C_(max) and C_0 were considerable. Nonlinear PK relationships were found from the doses of 540–900 mg of EC-MPS.

中国肝移植患者服用麦考酚钠肠溶片后霉酚酸及其代谢物的药动学研究

目的：探讨肝移植患者口服麦考酚钠肠溶片（EC-MPS）后不同阶段霉酚酸（MPA）及其代谢物的药动学特征。方法：采集24例肝移植患者服用EC-MPS后第1周和第3周0-12 h血标本,采用LC-MS/MS法测定MPA、7-O-葡萄糖醛酸结合代谢物（MPAG）、酰化葡萄糖醛酸代谢物（Ac MPAG）等血浆中药物浓度,采用非房室法计算药动学参数。结果：服用EC-MPS1周与3周后,MPA的Cmax、AUC0-12、t1/2分别为（18.1±8.75）与（20.7±16.0）μg·ml^-1、（42.7±17.5）与（47.1±23.9）μg·h·ml^-1、（3.33±2.81）与（3.30±1.89）h,其主要药动学参数在第1周与第3周无显著差异;Ac MPAG的Cmax、AUC0-12、t1/2分别为（2.50±1.86）与（1.78±1.72）μg·ml^-1、（14.5±11.7）与（6.97±6.57）μg·h·ml^-1、（4.48±2.53）与（3.76±1.89）h,给药后第1周Ac MPAG的AUC0-12显著高于第3周（P〈0.01）;MPAG的Cmax、AUC0-12、t1/2分别为（171.6±135.4）与（152.2±115.9）μg·ml^-1、（1 299±1 204）与（1 051±561）μg·h·ml^-1、（8.73±4.25）与（7.75±2.87）h,其主要药动学参数在第1周与第3周无显著差异。服用吗替麦考酚酯（MMF）与EC-MPS患者的MPA的Cmax、Tmax、t1/2存在显著差异（P〈0.05）;治疗3周后代谢物MPAG的Cmax、AUC0-12显著高于服用MMF的患者（P〈0.05）。结论：不同阶段MPA蓄积不明显,但代谢物体内暴露差异明显。与服用MMF的患者相比,EC-MPS吸收延缓,而体内暴露无差异。

吗替麦考酚酯片联合注射用甲泼尼龙琥珀酸钠治疗肾病综合征的效果评价

目的:探讨吗替麦考酚酯片联合注射用甲泼尼龙琥珀酸钠治疗肾病综合征(NS)的效果。方法:选取河南科技大学第一附属医院2019年3月—2020年2月收治的126例NS患者作为研究对象,采用随机数字表法分为常规组(n=63)和联合组(n=63),常规组采用注射用甲泼尼龙琥珀酸钠治疗,联合组于常规组基础上加用吗替麦考酚酯片治疗,比较两组临床疗效、炎性因子水平及不良反应。结果:治疗2个月结束时,联合组总缓解率高于常规组(P<0.05);联合组血清白细胞介素-6(IL-6)、白细胞介素-23(IL-23)、肿瘤坏死因子-α(TNF-α)水平低于常规组(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:吗替麦考酚酯片联合注射用甲泼尼龙琥珀酸钠治疗可降低NS患者炎症因子水平,提高临床治疗效果。