Mycophenolic acid pharmacokinetics in pediatric liver transplant recipients

Abstract

The aim of this study is to study mycophenolic acid (MPA) pharmacokinetics in stable pediatric liver transplant recipients and determine which times best represent the area under the concentration versus time curve (AUC) of MPA plasma concentrations. MPA pharmacokinetic profiles were determined in 21 liver transplant recipients (age, 2 to 15 years; 12 boys) administered mycophenolate mofetil (MMF) for at least 6 months. Ten patients were coadministered cyclosporine A (CsA), and 11 patients were coadministered tacrolimus (Tac). Plasma MPA levels were analyzed by enzyme-multiplied immunoassay technique in blood samples at 0, 0.33, 0.67, 1.25, 2, 3.5, 5, and 7 hours after MMF administration. The AUC of plasma concentrations to 7 hours (AUC 0-7 ) was calculated using the linear trapezoidal rule. MPA plasma trough concentration (C 0 ), maximal concentration, and AUC 0-7 values ranged 9-to 14-fold at a median of 1.

Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters

“…In children after kidney or liver transplantation, in a few studies the significant correlation between MPA C trough and AUC 12 was proved (Filler, 2004;Aw et al, 2003). It was also observed that in children after renal transplantation, MPA C trough correlated well with the value of AUC 12 only in patients receiving steroids (Tönshoff et al, 2011).…”

Sequential Determination of Pharmacokinetics and Pharmacodynamics of Mycophenolic Acid in Liver Transplant Patients Treated with Mycophenolate Mofetil

“…Most data on MPA pharmacokinetics in liver transplant recipients consist in the determination of either predose MPA concentration as the only parameter assessed (6,7,9) or MPA AUC measured only once at variable periods following transplantation (7,8). There is only one investigation in which MPA pharmacokinetic parameters were determined sequentially during the early postoperative period (from one to six weeks after liver transplantation) (10), although no specific information was given in the study on whether fixed or changing doses of MMF were administered.…”

Inmunodepresión en el período postoperatorio inmediato del trasplante hepático

“…Los efectos secundarios más frecuentes del MPA son las molestias gastrointestinales, entre las que predominan la diarrea, la leucopenia y, en menor grado, la trombopenia y anemia. Es posible que la monitorización en sangre del MPA pueda limitar los efectos secundarios del fármaco, aunque este hecho está por demostrar en estudios más amplios 19 . El MMF disminuye de forma significativa la incidencia de rechazo agudo tras el trasplante renal con respecto a la azatioprina 16,20 .…”