肾移植受者生理因素对霉酚酸体内暴露量的影响

Effects of Physiological Factors on Mycophenolic Acid Exposure in Renal Transplant Recipients

关键词:  霉酚酸  治疗药物监测  生理因素  药-时曲线下面积

Key words:  Mycophenolic acid  Therapeutic drug monitoring  Physiological factors  Area under drug-time curve

摘要:

目的：分析肾移植受者霉酚酸血药浓度监测结果，探讨生理因素对肾移植受者霉酚酸体内暴露量的影响。方法：采用回顾性研究方法，对本院肾移植科使用吗替麦考酚酯（MMF）治疗并测定浓度的住院患者进行信息归纳，从浓度分布情况，性别、体重、基因多态性、白蛋白和血红蛋白水平及肾脏功能等生理因素对霉酚酸暴露量的影响进行分析探讨。结果：女性受者的霉酚酸药-时曲线下面积（AUC0～12h）明显高于男性受者；大体重受者的霉酚酸AUC0～12h比小体重受者低；不同基因型的受者霉酚酸AUC0～12h无明显差异；白蛋白正常水平组受者霉酚酸AUC0～12h高于低蛋白组；轻度贫血、中度贫血和重度贫血组的霉酚酸AUC0～12h均高于正常组；中度贫血组和正常组差异性有统计学意义；肌酐清除率小于60mL·min-1者其霉酚酸AUC0～12h显著增加，肌酐清除率30-59mL·min-1组与正常组之间的差异性有统计学意义。结论：霉酚酸血药浓度受性别、体重、血清蛋白水平以及肾脏功能等多种生理因素的影响，个体化治疗时需要进行血药浓度监测。

Abstract:

OBJECTIVE To analyze the monitoring results of mycophenolic acid blood concentration in renal transplant recipients, and To investigate the effect of physiological factors on mycophenolic acid exposure in renal transplant recipients. METHODS A retrospective research method was used to summarize the information of inpatients treated with mycophenolate mofetil（MMF） and their concentrations were measured in the kidney transplantation department of our hospital. The effects of physiological factors such as concentration distribution, gender, body weight, gene polymorphism, albumin and hemoglobin levels and renal function on mycophenolic acid exposure were analyzed and discussed. RESULTS The area under drug-time curve(AUC0～12h)of mycophenolic acid in female recipients was significantly higher than that in male recipients. The AUC0～12h of mycophenolic acid in recipients with large body weight was lower than that in recipients with small body weight. There was no significant difference in AUC0～12h of mycophenolic acid in recipients with different genotypes. The AUC0～12h of mycophenolic acid was higher than that of the low protein group . The AUC0～12h of mycophenolic acid in the mild anemia, moderate anemia and severe anemia groups was higher than the normal group, the moderate anemia group and the normal group had significant differences . The AUC0～12h of mycophenolic acid increased significantly in recipients with creatinine clearance less than 60mL·min-1. The difference between creatinine clearance 30-59mL·min-1 group and the normal group was statistically significant. CONCLUSION The blood concentration of mycophenolic acid is affected by various physiological factors such as gender, body weight, serum protein level, and renal function. Blood concentration monitoring is required during individualized treatment.