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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Pharmacokinetics of mycophenolic acid in renal transplant patients with delayed graft function.
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Pharmacokinetics of mycophenolic acid in renal transplant patients with delayed graft function.

机译：麦考酚酸在肾移植功能延迟患者中的药代动力学。

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The pharmacokinetics of mycophenolic acid (MPA), the immunosuppressant form of the prodrug mycophenolate mofetil (MMF), and the primary glucuronide metabolite, MPAG, were characterized in renal transplant patients with delayed graft function using random effects piecewise linear models. Eight patients were evaluated after receiving their first and subsequent daily oral doses of 1.5 g mycophenolate mofetil twice daily on study days 1 (n = 8), 7 (n = 8), 14 (n = 5), 21 (n = 2), and 28 (n = 7). The area under the concentration-time curve from zero to 12 hours (AUC0-12) for MPA, MPAG, MPA free fraction, and free MPA were analyzed in serial plasma samples using validated high-performance liquid chromatography and ultrafiltration procedures. Random effects piecewise linear models, fit by maximum likelihood methods, were applied to AUC0-12 of MPA and MPAG, MPA free fraction, AUC0-12 of free MPA, and serum creatinine concentration, the index of renal function used in this study. Two hemodialysis sessions did not lower MPA plasma concentration, although some MPAG was removed. The AUC0-12 of MPA increased as a function of time, although it was not possible to fit a statistical model to the data due to considerable among-patient variation in the pattern of increase with time. The AUC0-12 of MPAG, MPA free fraction, and AUC0-12 of free MPA reached maximal values on day 7; each of these parameters had unique day 1 to 7 positive slope values and unique day 7 to 28 negative slope values. The average creatinine concentration was maximal at day 1 and a unique negative slope was obtained between days 7 and 28. Thus, this study provides statistical models for the alteration of AUC0-12 of MPAG, MPA free fraction, AUC0-12 of free MPA, and serum creatinine in renal transplant patients with delayed graft function. These results provide evidence that renal dysfunction is associated with altered pharmacokinetics of MPA, particularly increased AUC0-12 of MPAG, MPA free fraction, and AUC0-12 of free MPA. The perturbed pharmacokinetics normalized with improving renal function.
机译：使用随机效应分段线性模型，对肾移植术后延迟移植功能的患者，对麦考酚酸（MPA），前药麦考酚酸酯（MMF）的免疫抑制剂形式和主要葡萄糖醛酸代谢产物MPAG的药代动力学进行了表征。在研究第1天（n = 8），7（n = 8），14（n = 5），21（n = 2）的第一天和随后的每日口服剂量的1.5g霉酚酸酯Mofetil每日两次后，对八名患者进行了评估。和28（n = 7）。使用经验证的高效液相色谱和超滤程序，在连续血浆样品中分析了MPA，MPAG，MPA游离级分和游离MPA的浓度时间曲线从零到12小时的面积（AUC0-12）。通过最大似然法拟合的随机效应分段线性模型应用于MPA和MPAG的AUC0-12，MPA游离级分，游离MPA的AUC0-12和血清肌酐浓度（本研究中使用的肾功能指标）。尽管去除了一些MPAG，但两次血液透析仍未降低MPA血浆浓度。 MPA的AUC0-12随着时间的增加而增加，尽管由于患者之间随时间增加的模式存在很大差异，因此无法将统计模型拟合到数据中。 MPAG的AUC0-12，游离MPA分数和游离MPA的AUC0-12在第7天达到最大值。这些参数中的每个参数都有唯一的第1天到第7天正斜率值和唯一的第7天到28天负斜率值。第1天的平均肌酐浓度最高，并且在第7天到28天之间获得了唯一的负斜率。因此，本研究提供了统计模型，用于改变MPAG的AUC0-12，游离MPA的分数，游离MPA的AUC0-12，和血清肌酐在肾移植术后移植物功能延迟的患者中。这些结果提供了肾功能不全与MPA的药代动力学改变有关的证据，特别是MPAG的AUC0-12，MPA游离分数和游离MPA的AUC0-12增加。改善的肾功能使药物动力学趋于正常。

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