Ding C, Xue W, Tian P, Ding X, Pan X, Xiang H, Tian X, Li Y, Zheng J
Department of Renal Transplantation, Medical College of Xi'an Jiaotong University, Xi'an, China; Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China.
Int J Clin Pract Suppl. 2014 Apr(181):10-6. doi: 10.1111/ijcp.12401.
To investigate the pharmacokinetics of enteric-coated mycophenolate sodium (EC-MPS) and the clinical outcome in kidney transplant recipients in the early post-transplantation phase. Then explain which regimen is more suitable for Chinese renal transplant recipients.
In total, 60 de novo kidney transplant recipients treated with tacrolimus and steroids were randomised to receive EC-MPS at standard dose (SD; 1440 mg/day; n = 28) or low dose (LD; 1080 mg/day; n = 32). Efficacy parameters, safety and tolerability were assessed over a 6-month study period. Full mycophenolic acid (MPA) areas under the curve (AUCs) were completed on days 3 and 5, whereas a three-point limited sampling strategy (LSS) was utilised for MPA AUC assessments at 2 weeks and months 1, 3 and 6 (the LSS for three-time-point MPA AUC 0-12 h (mg h/l) = 15.99 + 0.87C1 h + 0.68C2 h + 7.85C4 h ; r(2) = 0.8670.
The mean AUC levels at day 3 and day 5 in the SD group were significantly higher than in the LD group (57.4 mg·h/l vs. 38.2 mg·h/l and 59.3 mg·h/l vs. 44.8 mg·h/l, respectively, p < 0.01). There was a trend for fewer clinically diagnosed acute rejections in the SD group vs. the LD group at 6 months (7.1% vs. 12.5%). This trend was also present when acute rejection was analysed as biopsy-proven cases. There were significantly more acute rejections (all definitions) in patients with MPA AUC levels < 30 mg·h/l compared with those with MPA AUC levels ≥ 30 mg·h/l within 6 months (p < 0.05). Renal function, incidence of infection and haematological disorders were not significantly different in either study group.
Early adequate MPA exposure in renal transplant recipients can be achieved with a higher starting dose. In addition, a SD regimen was as well-tolerated as a LD regimen. Furthermore, early adequate MPA exposure significantly lowered the rate of acute rejection without compromising safety and tolerability.
研究肾移植受者移植后早期肠溶型霉酚酸钠（EC-MPS）的药代动力学及临床结局。并解释哪种给药方案更适合中国肾移植受者。
总共60例接受他克莫司和类固醇治疗的初发肾移植受者被随机分为接受标准剂量（SD；1440毫克/天；n = 28）或低剂量（LD；1080毫克/天；n = 32）的EC-MPS。在为期6个月的研究期间评估疗效参数、安全性和耐受性。在第3天和第5天完成霉酚酸（MPA）的完整曲线下面积（AUC）测定，而在第2周、第1、3和6个月采用三点有限采样策略（LSS）进行MPA AUC评估（三点MPA AUC 0-12小时（毫克·小时/升）的LSS = 15.99 + 0.87C1小时 + 0.68C2小时 + 7.85C4小时；r² = 0.8670）。
SD组第3天和第5天的平均AUC水平显著高于LD组（分别为57.4毫克·小时/升对38.2毫克·小时/升和59.3毫克·小时/升对44.8毫克·小时/升，p < 0.01）。6个月时，SD组临床诊断的急性排斥反应趋势少于LD组（7.1%对12.5%）。当将急性排斥反应分析为活检证实的病例时，这种趋势也存在。与MPA AUC水平≥30毫克·小时/升的患者相比，MPA AUC水平< 30毫克·小时/升的患者在6个月内急性排斥反应（所有定义）显著更多（p < 0.05）。两个研究组的肾功能、感染发生率和血液系统疾病无显著差异。
肾移植受者通过更高的起始剂量可实现早期充分的MPA暴露。此外，SD给药方案与LD给药方案耐受性相当。此外，早期充分的MPA暴露显著降低了急性排斥反应的发生率，且不影响安全性和耐受性。
