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霉酚酸酯对肾移植受者血液学副作用发生率的影响。

Effect of mycophenolate mofetil on hematological side effects incidence in renal transplant recipients.

机构信息

Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznań, Poland.

出版信息

Clin Transplant. 2013 Jul-Aug;27(4):E407-14. doi: 10.1111/ctr.12164. Epub 2013 Jun 13.

Abstract

Mycophenolate mofetil (MMF), an immunosuppressant administered after solid organ transplantation, is generally well tolerated; however, it frequently causes hematological toxicity. In this study, we aimed to assess the relation between the pharmacokinetic parameters of MMF metabolites (mycophenolic acid [MPA] and 7-O-MPA glucuronide [MPAG]) and the adverse effects on the hematopoietic system in renal transplant recipients. The four-h pharmacokinetic profiles of MPA and MPAG were determined using the HPLC method for MMF-treated patients (n = 61) among 106 renal transplant recipients (during the late post-transplant period) participating in the study. Anemia was more frequently observed in the study group compared with the control group (30.7% vs. 20.0%) and although the difference was insignificant, plasma iron concentrations were significantly higher in patients treated with MMF (32.9 ± 9.4 μmol/L vs. 28.7 ± 9.4 μmol/L; p = 0.032). Iron supplementation was more frequently applied to patients with anemia (48.2%) compared with patients with hemoglobin within the norm (20.3%; p = 0.005). As all MPAG pharmacokinetic parameters correlated negatively with hemoglobin and hematocrit, and MPAG pharmacokinetic parameters were higher in patients with anemia, MPAG may be the predicting factor of MMF side effects. In renal transplant recipients, especially with deteriorated renal function, extensive iron supplementation may be ineffective as anemia was associated with declined renal function and was not caused by low iron concentration.

摘要

霉酚酸酯(MMF)是一种在实体器官移植后使用的免疫抑制剂,通常具有良好的耐受性;然而,它常引起血液学毒性。在这项研究中,我们旨在评估 MMF 代谢物(霉酚酸[MPA]和 7-O-MPA 葡萄糖醛酸苷[MPAG])的药代动力学参数与肾移植受者造血系统不良反应之间的关系。采用 HPLC 法测定了 106 例肾移植受者(移植后晚期)中 61 例 MMF 治疗患者(n=61)的 MPA 和 MPAG 的四小时药代动力学曲线。与对照组(30.7%比 20.0%)相比,研究组贫血的发生率更高,但差异无统计学意义,且 MMF 治疗患者的血浆铁浓度明显更高(32.9±9.4 μmol/L 比 28.7±9.4 μmol/L;p=0.032)。与血红蛋白正常的患者(20.3%)相比,贫血患者(48.2%)更常接受铁补充治疗(p=0.005)。由于所有 MPAG 药代动力学参数均与血红蛋白和血细胞比容呈负相关,且贫血患者的 MPAG 药代动力学参数更高,因此 MPAG 可能是 MMF 副作用的预测因素。在肾移植受者中,尤其是肾功能恶化者,广泛的铁补充可能无效,因为贫血与肾功能下降有关,而不是由铁浓度低引起。

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