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

Abstract

Objective To identify the effect of renal impairment on the pharmacokinetics of mycophenolate mofetil in Chinese adult renal recipients during the early post-transplant period. Methods Thirty 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. Results Mean 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). Conclusion In 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. Key words: Mycophenolic acid; Pharmacokinetics; Kidney transplantation