PMID- 18946804
OWN - NLM
STAT- MEDLINE
DCOM- 20090123
LR  - 20221207
IS  - 1366-5928 (Electronic)
IS  - 0049-8254 (Linking)
VI  - 38
IP  - 11
DP  - 2008 Nov
TI  - Influence of uridine diphosphate (UDP)-glucuronosyltransferases and ABCC2 genetic 
      polymorphisms on the pharmacokinetics of mycophenolic acid and its metabolites in 
      Chinese renal transplant recipients.
PG  - 1422-36
LID - 10.1080/00498250802488585 [doi]
AB  - The aim was to investigate the effect of UGT1A9, UGT1A8, UGT2B7 and ABCC2 
      polymorphism on the pharmacokinetics of mycophenolic acid (MPA) and its 
      metabolites phenolic glucuronide (MPAG) and acyl glucuronide (AcMPAG) in Chinese 
      renal transplant recipients. Single nucleotide polymorphisms (SNP) in 
      UGT1A9-118(dT)(9)/(10), UGT1A9 T-440C/C-331T, UGT1A8*3, UGT2B7 G211T, UGT2B7 
      C802T, ABCC2 C-24T, and ABCC2 G1249A were detected. A total of 46 recipients were 
      enrolled in the pharmacokinetics study at day 30 after kidney transplantation. 
      Differences in the MPA pharmacokinetic profiles confirmed large inter-patient 
      variation of MPA exposure. A statistical significant increase in the 
      dose-adjusted AUC(6-12) level of MPA was found in patients bearing the 
      -118(dT)(10) allele of the UGT1A9 gene (T(9) = 7.34 +/- 4.11 mg h ml(-1) g(-1); 
      T(9)/T(10) = 11.54 +/- 7.62 mg h ml(-1) g(-1); and T(10) = 11.89 +/-8.76 mg h 
      ml(-1) g(-1), p = 0.041). A similar trend was also observed for the dose-adjusted 
      AUC(0-12) and AUC(6-12) of MPAG. Patients carrying the heterozygous mutant 
      alleles of ABCC2 G1249A exhibited higher AUC(6-12)/D of AcMPAG than those with 
      wild-type genotype (p = 0.016). The other SNPs that were genotyped did not cause 
      any significant variation in MPA and MPAG pharmacokinetic parameters. In 
      conclusion, the enterohepatic recirculation of MPA in the patients seems to be 
      more extensive in UGT1A9-118(dT)(10) allele carriers, and the exposure of AcMPAG 
      is higher in patients carrying ABCC2 G1249A genotype than those with wild-type 
      genotype.
FAU - Zhang, W-X
AU  - Zhang WX
AD  - Institute of Clinical Pharmacology, Ruijin Hospital, Shanghai JiaoTong University 
      School of Medicine, Shanghai, China.
FAU - Chen, B
AU  - Chen B
FAU - Jin, Z
AU  - Jin Z
FAU - Yu, Z
AU  - Yu Z
FAU - Wang, X
AU  - Wang X
FAU - Chen, H
AU  - Chen H
FAU - Mao, A
AU  - Mao A
FAU - Cai, W
AU  - Cai W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Xenobiotica
JT  - Xenobiotica; the fate of foreign compounds in biological systems
JID - 1306665
RN  - 0 (ABCC2 protein, human)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glucuronides)
RN  - 0 (Multidrug Resistance-Associated Protein 2)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (UGT1A9 protein, human)
RN  - 54TS5J9T0K (mycophenolic acid glucuronide)
RN  - EC 2.4.1.- (UGT2B7 protein, human)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - EC 2.4.1.17 (UDP-Glucuronosyltransferase 1A9)
RN  - EC 2.4.1.17 (UDP-glucuronosyltransferase, UGT1A8)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - Adult
MH  - Asian People/genetics
MH  - Enzyme Inhibitors/*pharmacokinetics
MH  - Female
MH  - Genotype
MH  - Glucuronides/metabolism
MH  - Glucuronosyltransferase/*genetics/metabolism
MH  - Histocompatibility Testing
MH  - Humans
MH  - Kidney Transplantation
MH  - Male
MH  - Middle Aged
MH  - Multidrug Resistance-Associated Protein 2
MH  - Multidrug Resistance-Associated Proteins/*genetics/metabolism
MH  - Mycophenolic Acid/analogs & derivatives/metabolism/*pharmacokinetics
MH  - *Polymorphism, Genetic
MH  - UDP-Glucuronosyltransferase 1A9
EDAT- 2008/10/24 09:00
MHDA- 2009/01/24 09:00
CRDT- 2008/10/24 09:00
PHST- 2008/10/24 09:00 [pubmed]
PHST- 2009/01/24 09:00 [medline]
PHST- 2008/10/24 09:00 [entrez]
AID - 904709753 [pii]
AID - 10.1080/00498250802488585 [doi]
PST - ppublish
SO  - Xenobiotica. 2008 Nov;38(11):1422-36. doi: 10.1080/00498250802488585.