Linked Life Data

18946804

Source:http://linkedlifedata.com/resource/pubmed/id/18946804

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-11-6
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1366-5928
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1422-36
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Influence of uridine diphosphate (UDP)-glucuronosyltransferases and ABCC2 genetic polymorphisms on the pharmacokinetics of mycophenolic acid and its metabolites in Chinese renal transplant recipients.
pubmed:affiliation
Institute of Clinical Pharmacology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't