Pharmacokinetics of free and total mycophenolic acid in paediatric and adult renal transplant recipients: Exploratory analysis of the effects of clinical factors and gene variants.

Abstract

Clinical and genetic influencing factors on free fraction of mycophenolic acid (MPA) have rarely been discussed. The present study investigated whether the clinical and genetic factors could explain the variability in the pharmacokinetics of free MPA (fMPA) and total MPA (tMPA) in Chinese paediatric and adult renal transplant recipients. Twenty-eight paediatric and 31 adult patients were enrolled, and the concentrations of tMPA and fMPA were determined at 0 h (predose) and 0.5, 1, 1.5, 2, 4, 5, 8, 9, 10 and 12 h after mycophenolate mofetil administration. Genetic polymorphisms of UGTs (rs671448, rs1042597, rs2741049, rs62298861, rs7439366, rs12233719) and ABCC2 (rs717620) were simultaneously determined. The clinical and genetic data were analysed and reported. tMPA and fMPA concentrations adjusted for dose per body weight were consistently higher in adults than in paediatric patients. In the paediatric group, only albumin and time after transplantation correlated significantly with the MPA-free fraction variation, which could explain 32.4% of the variability. Besides, ABCC2 polymorphism, albumin and time after transplantation correlated significantly with the MPA-free fraction variation in adults, which could explain 56.9% of the variability. The influencing factors in the paediatric group are different from those in adults, which may be due to age-related transporter expression.