Impact of UGT1A9 Polymorphism on Mycophenolic Acid Pharmacokinetic Parameters in Stable Renal Transplant Patients

Abstract

There are wide individual differences in pharmacokinetic parameters of mycophenolate mofetil (MMF) among transplanted patients. Some studies have shown that single nucleotide polymorphisms (SNPs) of the Uridine Diphosphate Glucuronosyl Transferase1A9 (UGT1A9) are responsible for these differences in early days after transplantation. Therefore it was decided to evaluate the influence of UGT polymorphism on MMF pharmacokinetics among stable Iranian transplant patients. This was a cross sectional study from March 2008 through December 2008 in Imam Khomeini Hospital affiliated to the Tehran University of Medical Sciences in Iran. Blood samples were taken from 40 de novo stable Iranian renal transplant patients taking 2 g MMF daily with SrCr£1.4 mg/dL with at least 3 months history of transplantation. Appropriate PCR and HPLC methods were used for the determination of SNPs and their impact on MPA pharmacokinetics. T-275A polymorphism occurred in 15% of patients, UGT1A9*3 occurred in 2.5% of patients. Carriers of T-275A polymorphism had significant lower MPA AUC 0-12 in comparison with non-carriers or wild type (73.3±17.8 mg/h/mL vs. 110.8±31.1 mg/h/mL, p = 0.006). There was no significant difference in AUC 6-12 between the two groups although carriers of T-275A SNP had lower MPA AUC 6-12 (22.4±4.5 mg/h/mL vs. 26.8±10.2 mg/h/mL, p=0.24). Cmax was lower in the carriers of (20.2±9.0 mg/mL vs. 37.2±12.5 mg/mL, p=0.004). There was no significant difference in C0 between two groups. (3.0±1.2 mg/mL vs. 3.9±1.6 mg/mL, p=0.1). This study in Iranian stable transplanted patients shows that carriers of T-275A polymorphism had significantly lower MPA exposure compared to non-carriers.