Department of Nephrology, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Clin J Am Soc Nephrol. 2010 Mar;5(3):503-11. doi: 10.2215/CJN.06050809. Epub 2010 Feb 11.
Adequate early mycophenolic acid (MPA) exposure is an important determinant for effective rejection prophylaxis. This pharmacokinetic study investigated whether an intensified dosing regimen of enteric-coated mycophenolate sodium (EC-MPS) could achieve higher mycophenolic acid (MPA) exposure early after transplantation versus a standard dosing regimen.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: De novo kidney transplant recipients (n = 75) who were treated with basiliximab induction and cyclosporine were randomly assigned to receive EC-MPS as either standard dosing (1440 mg/d; n = 37) or intensified dosing (days 0 through 14: 2880 mg/d; days 15 through 42: 2160 mg/d; followed by 1440 mg/d; n = 38). Full 12-hour pharmacokinetic and pharmacodynamic profiles were taken at six time points during the first 3 months. Exploratory analysis of inosine monophosphate dehydrogenase (IMPDH) activity was also performed for better understanding of the pharmacokinetic-pharmacodynamic relationship between MPA exposure and IMPDH activity in the early posttransplantation period. Preliminary efficacy parameters, safety, and tolerability were assessed.
Exposure to MPA was significantly higher on days 3 and 10 after transplantation in the intensified versus standard EC-MPS group, with 52.9 versus 22.2% (P < 0.05) of patients reaching MPA exposure >40 mg/h per L in the first week. The intensified regimen resulted in significantly lower IMPDH activity on day 3 after transplantation, and the overall safety was comparable for both groups.
These pharmacokinetic and safety data support further research on the hypothesis that early adequate MPA exposure could improve clinical outcome.
充分的早期霉酚酸（MPA）暴露是有效预防排斥反应的重要决定因素。这项药代动力学研究旨在探讨肠溶剂型麦考酚酸钠（EC-MPS）强化剂量方案与标准剂量方案相比，是否能在移植后早期获得更高的 MPA 暴露。
设计、地点、参与者和测量：接受巴利昔单抗诱导和环孢素治疗的新诊断肾移植受者（n=75）被随机分为 EC-MPS 标准剂量组（1440mg/d；n=37）或强化剂量组（第 0 天至第 14 天：2880mg/d；第 15 天至第 42 天：2160mg/d；随后为 1440mg/d；n=38）。在移植后前 3 个月的 6 个时间点采集了完整的 12 小时药代动力学和药效动力学曲线。还进行了肌苷单磷酸脱氢酶（IMPDH）活性的探索性分析，以更好地理解 MPA 暴露与移植后早期 IMPDH 活性之间的药代动力学-药效学关系。评估了初步疗效参数、安全性和耐受性。
强化 EC-MPS 组在移植后第 3 天和第 10 天的 MPA 暴露显著高于标准 EC-MPS 组，第 1 周内有 52.9%（P<0.05）的患者达到 MPA 暴露>40mg/h/L。强化方案导致移植后第 3 天的 IMPDH 活性显著降低，两组的总体安全性相当。
这些药代动力学和安全性数据支持进一步研究假设，即早期充分的 MPA 暴露可能改善临床结果。
