供体因素对肾移植术后早期霉酚酸及其代谢物药代动力学的影响

Influence of donor physiological condition on pharmacokinetics of mycophenolic acid and its metabolite in the early period after renal transplantation

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 influence of the physiological conditions and kidney function of the donors on their recipients＇ mycophenolic acid（ MPA） and mycophenolic acid glucuronide（ MPAG） levels in the early period after renal transplantation. Methods Forty-two patients receiving mycophenolate mofetil（ MMF） and 23 patients receiving enteric-coated mycophenolate sodium（ EC-MPS）,as well as their donors were included in this study. For patients who recieving MMF,MPA and MPAG concentrations were detected by HPLC,then AUC_（MPA）and AUC_MPAGwere calculated by the limited sampling strategy（ LSS） model established by our lab previously. For the patients receiving EC-MPS,AUC_（MPA）and AUC_MPAGwere calculated by linear trapezoidal rule. Results Spearman test showed significant correlation between recipients＇ AUC_MPAG and the age of donors in MMF group,EC-MPS group and the total cohort（ P〈0. 05）. Moreover,AUC_MPAGin the recipients of elder group（ 〉55 yearsold） was significantly higher than that in the younger group（ ≤55 years old） in both MMF group and the total cohort（ P〈0. 05）. In addition,AUC_MPAGwas siginificantly associated with the urea levels of donors before renal transplantation in MMF group and the total cohort（ P〈0. 05）. Patients were divided into tacrolimus（ FK506） or cyclosporin A（ CsA） group according to their comedication. AUC_MPAGwas significantly higher in CsA group than that in FK506 group（ P〈0. 01）. AUC_MPAGin the recipients of elder group was significantly higher than that in the younger group（ P〈0. 05）,and AUC_MPAGwas siginificantly associated with the urea levels of donors in FK506 group（ P〈0. 05）. In CsA group,significant correlation between AUC_MPAGand the age of donors was showed（ P〈0. 05）. Conclusion Our data suggested that the age and the urea level of donors might play roles in the recipients＇ MPAG exposure in the early period after renal transplantation.