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1. Clin Chim Acta. 2011 Dec 22. [Epub ahead of print]

The association of the UGT1A8, SLCO1B3 and ABCC2/ABCG2 genetic polymorphisms with
the pharmacokinetics of mycophenolic acid and its phenolic glucuronide metabolite
in Chinese individuals.

Fang G, Zheng J, Yi-Jun D, Xiao-Yan Q, Jun-Jie D, Xiao-Jin S, Zhong-Dong L,
Ming-Kang Z.

Clinical Pharmacy Laboratory, Huashan Hospital, Fudan University, Shanghai,
People's Republic of China.

BACKGROUND: This study aimed to evaluate the effect of UGT1A8*2, SLCO1B3 T334G,
ABCC2 C-24T and ABCG2 C421A polymorphisms on the pharmacokinetics (PKs) of
mycophenolic acid (MPA) and its phenolic glucuronide (MPAG) in healthy Chinese
volunteers and in stable renal transplant patients. METHODS: The data were
extracted from comparative bioavailability studies conducted in 42 healthy
individuals and 37 renal transplant patients. A complete PK profile was obtained
over 48h for healthy volunteers and over 12h for the transplant patients. The
MPA/MPAG plasma concentrations were measured by HPLC. The genotypes were
determined using either the Taqman probe technique or direct sequencing. A
multivariate analysis was used to assess the effect of the genotypes (UGT1A8*2,
SLCO1B3 T334G, ABCC2 C-24T and ABCG2 C421A) and other covariates (age, weight,
height, calculated creatinine clearance, serum albumin, haemoglobin and drug
comedication) on the AUC(4-12) and AUC(0-12) for MPA and MPAG in the healthy
volunteers and patients. RESULTS: In the healthy volunteers, the dose-adjusted
geometric means (GM) of the MPA AUC(4-12) in individuals with the SLCO1B3 334T
allele were 30.4% lower than those values in the 334G homozygote carriers
(P<0.05); in the transplant patients, the steroid dose was associated with a
negative effect on the AUC of MPAG (P<0.03) and weight was associated with a
negative effect on the AUC for MPA in the healthy volunteers and patients
(P<0.03). No other significant effect of genotype or of the other studied
variables on AUC(4-12) or AUC(0-12) of MPA/MPAG was found in the healthy
volunteers or patients. CONCLUSIONS: The PKs of MPA is affected by the SLCO1B3
polymorphism in healthy Chinese individuals. The absence of an effect of SLCO1B3
polymorphisms in transplant patients may be due to the co-administration of
cyclosporine (CsA). Concomitant steroid dose and weight are two important
covariates of the AUC of MPA and MPAG, which should be taken into account in
clinical use. Further confirmatory in vivo studies are needed.

Copyright © 2011 Elsevier B.V. All rights reserved.

PMID: 22227166 [PubMed - as supplied by publisher]