Effect of hepatic drug transporter polymorphisms on the pharmacokinetics of mycophenolic acid in patients with severe renal dysfunction before renal transplantation

Abstract

1. The objective of this study was to examine the association of UGT1A9, SLCO, and ABCC polymorphisms with mycophenolic acid (MPA) pharmacokinetics in ABO blood type (ABO) incompatible patients with severe renal dysfunction pre-transplantation.2. In all patients, on day 14 after beginning mycophenolate mofetil (MMF) treatment (1 week before transplantation) and on day 28 after renal transplantation, samples were collected just prior to and 1, 2, 3, 4, 6, 9, and 12 h after oral MMF administration.3. The median dose-adjusted AUC0–12 of MPA after renal transplantation was significantly lower than before transplantation (57.9 versus 76.5 μg h/mL, respectively, p = 0.002).4. Although the enterohepatic circulation of MPA pre-transplantation was extremely high (57.6%), this level was significantly reduced after renal transplantation (34.6%).5. In the multivariate analysis, pre-transplantation, patients with the SLCO1B3 334T allele (p = 0.003), higher alanine aminotransferase (p = 0.002), and lower body weight were independently predictive for a higher dose-adjusted AUC0–12 of MPA.6. In patients with severe renal dysfunction pre-transplantation, MPA is excreted mainly to bile from the liver, and as a consequence, the SLCO1B3 334T > G polymorphism was found to be significantly associated with MPA exposure.