Effect of hepatic drug transporter polymorphisms on the pharmacokinetics of mycophenolic acid in patients with severe renal dysfunction before renal transplantation.
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 AUC0-12of 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 AUC0-12of 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.
a Department of Pharmacy , Akita University Hospital , Akita , Japan.
Hideaki
H
Kagaya
a Department of Pharmacy , Akita University Hospital , Akita , Japan.
Takenori
T
Niioka
b Department of Urology , Akita University School of Medicine , Akita , Japan , and.
Mitsuru
M
Saito
b Department of Urology , Akita University School of Medicine , Akita , Japan , and.
Takamitsu
T
Inoue
b Department of Urology , Akita University School of Medicine , Akita , Japan , and.
Kazuyuki
K
Numakura
b Department of Urology , Akita University School of Medicine , Akita , Japan , and.
Tomonori
T
Habuchi
c Center for Kidney Disease and Transplantation, Akita University Graduate School of Medicine , Akita , Japan.
Shigeru
S
Satoh
a Department of Pharmacy , Akita University Hospital , Akita , Japan.
Masatomo
M
Miura
D019540:Area Under Curve; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000493:pharmacokinetics*; D020641:Polymorphism, Single Nucleotide; D000090264:UDP-Glucuronosyltransferase 1A9
D007166:Immunosuppressive Agents; C000715591:UGT1A9 protein, human; D014453:Glucuronosyltransferase; D000090264:UDP-Glucuronosyltransferase 1A9; D009173:Mycophenolic Acid
Mycophenolic acid; SLCO1B3 334T > G polymorphism; pharmacokinetics; pre-transplantation; renal transplantation