Document Detail


Biotransformation enzymes and drug transporters pharmacogenetics in relation to immunosuppressive drugs: impact on pharmacokinetics and clinical outcome.
MedLine Citation:
PMID:  18401258     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Immunosuppressive drugs commonly used after organ transplantation to prevent acute rejection including tacrolimus, cyclosporine, sirolimus, and mycophenolic acid are characterized by a narrow therapeutic index and broad interindividual variability in their pharmacokinetics. Adequate immunosuppression aims to reach an optimal benefit-risk ratio. Therapeutic drug monitoring represents a crucial step in routine practice to maintain blood concentrations within the target window, because the bioavailability of these drugs depends on their absorption, distribution, biotransformation, and elimination. Single nucleotide polymorphisms (SNPs) in genes encoding biotransformation enzymes (CYP3A) and drug transporters (ABCB1) have opened up a promising way for the selection of individual dosages. The relationship of these SNPs with immunosuppressive drug pharmacokinetics was extensively studied after kidney, liver, heart, and lung transplantations. Patient susceptibility to nephrotoxicity in the long term was also reported in relation to some SNPs, which could allow effective assessment of individual risk and selection of treatment according to patient parameters. Further studies are needed to provide evidence that a genetic analysis combined with therapeutic drug monitoring has the potential to optimize drug use after transplantation.
Authors:
Michel Mourad; Pierre Wallemacq; Martine De Meyer; Jacques Malaise; Luc De Pauw; Djamila Chaïb Eddour; Eric Goffin; Jan Lerut; Vincent Haufroid
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Transplantation     Volume:  85     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-10     Completed Date:  2008-06-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  S19-24     Citation Subset:  IM    
Affiliation:
Department of Surgery, Surgery and Abdominal Transplantation Division, Université Catholique de Louvain, Saint Luc University Hospital, Brussels, Belgium. michel.mourad@chir.ucl.ac.be
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MeSH Terms
Descriptor/Qualifier:
Biotransformation / genetics
Cytochrome P-450 Enzyme System / genetics,  metabolism
Graft Rejection / drug therapy,  prevention & control*
Humans
Immunosuppressive Agents / pharmacokinetics*,  therapeutic use
Kidney Transplantation
P-Glycoprotein / genetics,  metabolism
Pharmacogenetics*
Polymorphism, Single Nucleotide / genetics
Treatment Outcome
Chemical
Reg. No./Substance:
0/ABCB1 protein, human; 0/Immunosuppressive Agents; 0/P-Glycoprotein; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/CYP3A protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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