Effect of Time after Transplantation on Mycophenolic Acid Pharmacokinetic in Kidney Transplant Patients in Iran

Abstract

Purpose: Mycophenolic acid (MPA), the active metabolite of mycophenolate mofetil (MMF), exerts its immunosuppressive action by blocking T and B-cell proliferation via inhibition of inosine monophosphate dehydrogenase (IMPDH). Various factors affect MPA pharmacokinetic (PK) including renal function, concomitant immunosuppressant, serum protein level. Demographic data provide evidence for significant interpatient variability of MPA-PK parameters. Recent studies suggest that one of these affecting factors is uremic condition in early phase after transplantation. The aim of this study is to investigate the effect of time after transplantation on MPA-PK. Methods: In this study 19 patients in early phase post transplant period with normal graft function (GFR>70 ml/min), who fulfilled inclusion & exclusion criteria were selected. Blood sampling in different times were taken in early phase and six months after transplantation (stable phase). MPA plasma concentrations were measured by reverse phase high performance liquid chromatography (HPLC). MPA-PK parameters were calculated in both states. Multiple stepwise regression analysis was used to determine the minimal and convenient time points of MPA levels that could be used to drive model equation best fitted to MPA AUC0-12 in both states. Results and conclusion: Our results showed that the MPA-AUC (area under the curve) and clearance was not affected by time but MPA-tmax was significantly lower in stable phase compared with early phase (P=0.001). The best regression equation for AUC estimation in early phase was (AUC = 0.904 C1.5 + 1.955 C4 + 10.206 C10 + 8.32) and in stable phase was (AUC = 0.663C6+4.945C10+1.074C2+0.536C1+2.11 5C0+3.945). Hence, Pharmacokinetic of MPA could be affected by time after transplantation.