Polymorphisms of UGT1A9 and UGT2B7 influence the pharmacokinetics of mycophenolic acid after a single oral dose in healthy Chinese volunteers.

PURPOSE: To explore the impact of UDP-glucuronosyltransferase polymorphisms (UGT1A9-118(dT) 9/10 , UGT1A9 CI399T, UGT1A9 C-440T and UGT2B7 G211T) on the pharmacokinetics of mycophenolic acid (MPA) in healthy Chinese volunteers.

METHODS: We recruited ten healthy volunteers with no polymorphisms (control group), 11 homozygotes of mutants UGT1A9 CI399T and UGT1A9-118(dT) 9/10 , ten heterozygotes of UGT1A9 C440T and seven carriers of UGT2B7 211T from a total of 518 healthy Chinese volunteers. All the volunteers were orally administered a single dose of 1.5 g mycophenolate mofetil (MMF) after an overnight fast. Plasma was then collected 72 h after MMF administration. MPA, MPA-7-O-glucuronide (MPAG) and its acylglucuronide (AcMPAG) were detected by ultra-pressure liquid chromatography with UV detection.

RESULTS: Compared with the control group, the UGT1A9 CI399T and UGT1A9-118(dT) 9/10 mutant homozygotes had higher MPAG plasma concentrations. Subjects with UGT1A9-440TC had enhanced MPA exposure while carriers of UGT2B7 211T had higher concentrations of the toxic metabolite, AcMPAG.

CONCLUSIONS: The current results indicate that UGT1A9 and UGT2B7 genotypes could significantly alter MPA pharmacokinetics in healthy Chinese volunteers after a single oral dose of MMF.