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目的探讨供体因素对肾移植术后早期霉酚酸(MPA)及其代谢物(MPAG)药代动力学的影响。方法纳入42例服用霉酚酸酯(MMF)患者以及23例服用霉酚酸钠肠溶片(EC-MPS)患者及其供体进行研究。用高效液相色谱法检测患者行活体肾移植术后早期患者霉酚酸及其代谢物的血浆药物浓度,霉酚酸酯组采用本实验室前期建立的有限检样法计算AUC_(MPA)及AUC_(MPAG),霉酚酸钠肠溶片组用线性梯形面积法计算AUC_(MPA)及AUC_(MPAG)。分析供体生理条件及肾功能与肾移植受体术后早期体内药物水平的相关性。结果供体年龄与霉酚酸酯组、霉酚酸钠肠溶片组和全体患者术后早期MPAG水平均呈正相关(P<0.05);霉酚酸酯组及全体患者中,高龄供体(>55岁)组患者术后早期MPAG水平显著高于非高龄供体(≤55岁)组的患者(P<0.05)。受体术前的尿素氮水平在霉酚酸酯组和全体患者中与受体术后早期MPAG水平呈正相关(P<0.05)。根据联合用药方案将患者分为他克莫司(FK506)组和环孢素A(Cs A)组,Cs A组患者AUC_(MPAG)显著高于FK506组(P<0.01),FK506组中高龄供体组术后早期AUC_(MPAG)显著高于非高龄供体组(P<0.05),供体术前的尿素氮水平与患者术后早期AUC_(MPAG)呈显著正相关(P<0.05);Cs A组中供体年龄与患者术后早期AUC_(MPAG)呈显著正相关(P<0.05)。结论供体年龄与术前尿素氮水平是肾移植受体术后早期霉酚酸代谢物水平的重要影响因素。
Objective To investigate the effect of donor factors on the pharmacokinetics of early mycophenolic acid (MPA) and its metabolites (MPAG) after renal transplantation. Methods Forty-two patients with mycophenolate mofetil (MMF) and 23 patients with mycophenolate mofetil (EC-MPS) and their donors were included in the study. Plasma concentrations of mycophenolic acid and its metabolites in patients with early renal transplant recipients were determined by HPLC. Mycophenolate mofetil group was used to calculate the AUC MPA and AUC_ (MPAG) and mycophenolate sodium enteric-coated tablets were used to calculate AUC_ (MPA) and AUC_ (MPAG) using linear trapezoidal area method. The correlation between donor physiological conditions and renal function and early postoperative drug levels in renal transplant recipients was analyzed. Results There was a positive correlation between donor age and MPAG levels in mycophenolate mofetil and mycophenolate enteric-coated tablets group and in all patients (P <0.05). Among the patients with mycophenolate mofetil and all the patients, > 55 years old group was significantly higher than those in non-senior donors (≤55 years old group) (P <0.05). Preoperative urea nitrogen levels in patients with mycophenolate mofetil and all patients were positively correlated with the level of early postoperative MPAG (P <0.05). According to the combination regimen, the patients were divided into FK506 group and CsA group. The AUC MPAG of CsA group was significantly higher than that of FK506 group (P <0.01) The level of AUC MPAG in donor group was significantly higher than that in non-senior donor group (P0.05), and there was a significant positive correlation between preoperative urea nitrogen level and AUC MPAG in donor group (P0.05) There was a significant positive correlation between donor age and MPAG in CsA group (P <0.05). Conclusion Donor age and preoperative urea nitrogen level are important influencing factors of early postoperative mycophenolic acid metabolites in renal transplant recipients.