Open AccessBiotransformation Enzymes and Drug Transporters Pharmacogenetics in Relation to Immunosuppressive Drugs: Impact on Pharmacokinetics and Clinical Outcome
Author(s) -
Michel Mourad,
Pierre Wallemacq,
Martine De Meyer,
Jacques Malaise,
Luc De Pauw,
Djamila Chaïb Eddour,
Éric Goffin,
Jan Lerut,
Vincent Haufroid
Publication year - 2008
Publication title -
transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.45
H-Index - 204
eISSN - 1534-6080
pISSN - 0041-1337
DOI - 10.1097/tp.0b013e318169c380
Subject(s) - pharmacology , pharmacokinetics , pharmacogenetics , therapeutic drug monitoring , drug , tacrolimus , medicine , mycophenolic acid , immunosuppressive drug , single nucleotide polymorphism , therapeutic index , kidney transplantation , transplantation , biology , genotype , gene , biochemistry
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.