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European Journal of Clinical Pharmacology

, Volume 63, Issue 3, pp 279–288 | Cite as

Influence of UGT1A8 and UGT2B7 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients

  • Hideaki Kagaya
  • Kazuyuki Inoue
  • Masatomo MiuraEmail author
  • Shigeru Satoh
  • Mitsuru Saito
  • Hitoshi Tada
  • Tomonori Habuchi
  • Toshio Suzuki
Pharmacokinetics and Disposition

Abstract

Objective

UGT1A8 and UGT2B7 are important uridine diphosphate-glucuronosyltransferase isoforms for the glucuronidation of mycophenolic acid (MPA). The aim of this investigation was to elucidate MPA pharmacokinetics in UGT1A8 and UGT2B7 genotypes in Japanese renal transplant recipients.

Methods

Seventy-two recipients received repeated doses of mycophenolate mofetil and tacrolimus. On day 28 after renal transplantation, plasma MPA concentrations were measured for the next 24 h using high-performance liquid chromatography. UGT1A8*2 (A173G) and UGT2B7*2 (Y268) were detected using a PCR-RFLP-based procedure.

Results

There were no significant differences in daytime and nighttime pharmacokinetics of MPA between UGT1A8 or UGT2B7 genotypes. The mean daytime dose-adjusted AUC0–12 of MPA in UGT1A8*1/*1, *1/*2 and *2/*2 were 2.47, 2.33 and 2.57 ng·h/ml/mg/kg (P = 0.7711), and the mean nighttime AUC0–12 were 2.15, 2.00 and 2.08 ng·h/ml/mg/kg (P = 0.4656). The mean daytime and nighttime dose-adjusted AUC0–12 of MPA in UGT2B7*1/*1, *1/*2 and *2/*2 were 2.61, 2.24 and 2.03 ng·h/ml/mg/kg and 2.18, 1.94, and 1.45 ng·h/ml/mg/kg, respectively (P = 0.3475 and 0.2575). The mean nighttime Cmax, tmax, and AUC6–12/AUC0–12 ratio (enterohepatic circulation and recirculation ratio) of MPA in all UGT1A8 and UGT2B7 genotypes were lower, longer, and higher, respectively, than the daytime values.

Conclusions

Both UGT1A8 and UGT2B7 allelic variants seem not to affect Japanese interindividual variability for plasma MPA concentration. Regardless of UGT1A8 and UGT2B7 genetic polymorphisms, the absorption of MPA through enterohepatic recirculation is higher at night.

Keywords

Mycophenolic acid UGT1A8 UGT2B7 Polymorphism Kinetics 

Notes

Acknowledgements

This work was supported by a grant (No.18923015) from the Japan Society for the Promotion of Science, Tokyo, Japan.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Hideaki Kagaya
    • 1
  • Kazuyuki Inoue
    • 1
  • Masatomo Miura
    • 1
    Email author
  • Shigeru Satoh
    • 2
  • Mitsuru Saito
    • 2
  • Hitoshi Tada
    • 1
  • Tomonori Habuchi
    • 2
  • Toshio Suzuki
    • 1
  1. 1.Department of PharmacyAkita University HospitalAkitaJapan
  2. 2.Department of UrologyAkita University School of MedicineAkitaJapan

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