早期移植肾功能不良受者吗替麦考酚酯的浓度一时间曲线下面积研究

Impact of renal impairment on pharmacokinetics of mycophenolate mofetil in chinese adult renal transplant recipients early after kidney transplantation

目的研究成人肾移植后早期肾功能不良情况下吗替麦考酚酯（MMF）的药物代谢动力学特点。方法30例成人肾移植受者，采用MMF联合他克莫司、泼尼松的三联免疫抑制方案。根据术后第30天移植肾功能分为3组：移植肾功能正常组（Ⅰ组，9例），估算肾小球滤过率（eGFR）≥90 ml·min－1·1.73 m－2；移植肾功能轻中度不全组（Ⅱ组，12例），30 ml·min－1·1.73 m－2≤eGFR〈90 ml·min－1·1.73 m－2；移植肾功能重度不全组（Ⅲ组，9例），eGFR〈30 ml·min－1·1.73 m－2。采用高效液相色谱法测定各组外周血麦考酚酸（MPA）及其代谢物麦考酚酸葡糖苷酸（MPAG）浓度，比较各组间MPA和MPAG的药物代谢动力学参数的差异。结果Ⅰ组和Ⅱ组的MPA 0～12 h药物浓度-时间曲线下面积（MPA-AUC0-12）分别为（37.8±15.6）μg·h·ml－1和（54.5±27.0）μg·h·ml－1，差异无统计学意义（P〉0.05）。Ⅲ组的MPA-AUC0-12明显高于Ⅰ组（P〈0.05），分别为（75.7±29.5）μg·h·ml－1和（37.8±15.6）μg·h·ml－1。Ⅲ组的MPAG-AUC0-12明显高于Ⅰ组和Ⅱ组（均P〈0.05），依次分别为（1899.1±987.1）μg·h·ml－1、（692.6±384.8）μg·h·ml－1和（859.9±261.4）μg·h·ml－1；Ⅰ组和Ⅱ组间MPAG-AUC0-12的差异无统计学意义（P＝0.532）。结论肾移植后早期重度移植肾功能不全伴少尿或无尿时，受者血总MPA水平显著增高，需注意调整药物剂量以减少相关不良反应。

ObjectiveTo identify the effect of renal impairment on the pharmacokinetics of mycophenolate mofetil in Chinese adult renal recipients during the early post-transplant period.MethodsThirty Chinese renal allograft recipients treated with mycophenolate mofetil in combination with tacrolimus and corticosteroids were divided into three groups based on their renal functions. Group Ⅰ had preserved renal function （eGFR≥90 mL/min/1.73 m2,n=9）; Group Ⅱ had moderate renal insufficiency （30≤eGFR〈90 mL/min/1.73 m2,n=12） and Group Ⅲ had severe renal impairment （eGFR 〈30 mL/min/1.73 m2,n=9）. mycophenolic acid （MPA） exposure and MPA glucuronide （MPAG） exposure were determined by high performance liquid chromatography （HPLC） at first month after transplantation. MPA-AUC0-12h and MPAG-AUC0-12h were calculated by the linear trapezoidal rule.ResultsMean MPA-AUC0-12h values were similar between group Ⅰ and group Ⅱ （37.8±15.6 vs. 54.5±27.0 μg·h·ml-1,P〉0.05）. MPA-AUC0-12h values were significantly higher in group Ⅲ than in group Ⅰ （75.7±29.5 vs. 37.8±15.6 μg·h·ml-1,P〈0.05）. The severe renal insufficiency group showed a significantly increased AUC0-12h for MPAG （1899.1±987.1 μg·h·ml-1 vs. 859.9±261.4 vs. 692.6±384.8, P〈0.05）. There was no significant difference in MPAG-AUC0-12h between group II and Group Ⅰ （P=0.532）.ConclusionIn adult renal recipients during the early post-transplant period, total MPA exposure was significantly increased because of severe renal insufficiency with oliguria or anuria. Adjusting MMF dose according to renal function may help to prevent side effects and improve efficacy.