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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-6-11
pubmed:abstractText
The present study investigated pharmacogenetic associations of common cytochrome P450 3A (CYP3A5 and CYP3A4) polymorphisms with dose requirements of calcineurin inhibitors, cyclosporine (CsA) and tacrolimus (Tac) in renal transplant recipients of North India. Two hundred twenty four patients on CsA and 73 patients on Tac-based immunosuppression regimen were genotyped for CYP3A5*3 (6986A>G) and CYP3A4*1B (-290A>G) and correlated with CsA/Tac dose requirement (mg/kg/day) and dose-adjusted CsA (C(2))/Tac (T (0)) blood levels (concentration/dose ratio) at 1 month and 3 months posttransplantation. The dose-adjusted levels were significantly lower in CYP3A5 expressers for CsA (p = 0.037; 3 months) and Tac (p < 0.001; 1 month and p < 0.001; 3 months) compared to the non-expressers, suggesting that for a given dose their CsA/Tac blood concentration is lower. The CYP3A5 non-expresser genotype was associated with reduced risk for allograft rejection (HR-0.18, 95% CI 0.03-0.99). No influence of CYP3A4*1B on CsA/Tac pharmacokinetics was observed. CYP3A5 expressers were associated with significantly lower dose-adjusted CsA/Tac concentrations and higher allograft rejection episodes in patients on Tac therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1432-1912
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
380
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
169-77
pubmed:meshHeading
pubmed-meshheading:19343327-Adolescent, pubmed-meshheading:19343327-Adult, pubmed-meshheading:19343327-Calcineurin, pubmed-meshheading:19343327-Child, pubmed-meshheading:19343327-Cyclosporine, pubmed-meshheading:19343327-Cytochrome P-450 CYP3A, pubmed-meshheading:19343327-Dose-Response Relationship, Drug, pubmed-meshheading:19343327-Female, pubmed-meshheading:19343327-Follow-Up Studies, pubmed-meshheading:19343327-Graft Rejection, pubmed-meshheading:19343327-Humans, pubmed-meshheading:19343327-Immunosuppressive Agents, pubmed-meshheading:19343327-India, pubmed-meshheading:19343327-Kidney Transplantation, pubmed-meshheading:19343327-Male, pubmed-meshheading:19343327-Middle Aged, pubmed-meshheading:19343327-Polymorphism, Single Nucleotide, pubmed-meshheading:19343327-Retrospective Studies, pubmed-meshheading:19343327-Tacrolimus, pubmed-meshheading:19343327-Time Factors, pubmed-meshheading:19343327-Young Adult
pubmed:year
2009
pubmed:articleTitle
Impact of CYP3A5 and CYP3A4 gene polymorphisms on dose requirement of calcineurin inhibitors, cyclosporine and tacrolimus, in renal allograft recipients of North India.
pubmed:affiliation
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't