Genetic polymorphisms of CYP3A genes affect cyclosporine a blood concentration and dose requirement in transplant recipients

Détails

ID Serval
serval:BIB_1DF48FD34AEB
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Institution
Titre
Genetic polymorphisms of CYP3A genes affect cyclosporine a blood concentration and dose requirement in transplant recipients
Titre de la conférence
NA
Auteur(s)
Crettol Séverine, Venetz Jean-Pierre, Aubert John-David, Fontana Massimiliano, Brocard Murielle, Pascual Manuel, Eap Chin-Bin
ISSN
0041-1337
Statut éditorial
Publié
Date de publication
2006
Peer-reviewed
Oui
Volume
82
Série
Transplantation
Pages
197
Langue
anglais
Notes
SAPHIRID:64702
Résumé
Cyclosporine A (CsA), mainly metabolized by cytochrome P450 (CYP) 3A, presents a wide interindividual variability in its kinetics. CYP3A4 and CYP3A5 are members of the CYP3A family. The presence of two CYP3A5*3 alleles results in an absence of CYP3A5 activity (CYP3A5 non expressors), while that of CYP3A4*1B allele results in an increased CYP3A4 activity. Our aim was to study the influence of CYP3A5*3 and CYP3A4*1B polymorphisms on CsA daily dose and trough blood concentrations. CsA daily dose and trough blood concentrations (measured by EMIT) were obtained at month 1, 3, 6 and 12 after transplantation from 70 Caucasian, renal or lung transplant recipients. CYP3A5*3 and CYP3A4*1B genotypes were determined by TaqMan. Log-transformed data from genotype groups were compared by t-test. CsA dose and weight-adjusted trough concentrations were significantly higher in CYP3A5 non expressors (*3/*3; n=56-59) than in CYP3A5 expressors (*1/*1 and *1/*3; n=10-11). CYP3A5 non expressors presented a 1.3-fold (CI95%=1.0-1.6; p=0.04), 1.6-fold (CI95%=1.3-2.1; p=0.0005) and 1.3-fold (CI95%=1.0-1.6; p=0.04) increase in dose and weight-adjusted trough concentrations at 3, 6 and 12 months after transplantation, respectively. Furthermore, CsA dose requirements were significantly higher in CYP3A5 expressors than in CYP3A5 non expressors. CYP3A5 expressors presented a 1.3-fold (CI95%=1.0-1.6; p=0.02), 1.3-fold (CI95%=1.1-1.7; p=0.01), 1.4- fold (CI95%=1.1-1.7; p=0.006) and 1.5-fold (CI95%=1.2-1.8; p=0.001) increase in CsA daily dose per weight at 1, 3, 6 and 12 months after transplantation, respectively. The three CYP3A4 *1/*1B patients presented significantly lower CsA dose and weight-adjusted trough concentrations (0.6-fold at 12 months; p=0.02) and higher daily doses (2-fold at 12 months; p=0.0007), but since they were all CYP3A5 expressors, no statement can be made. In conclusion, these data indicate that genotyping of CYP3A5 allele could be a useful tool, combined with therapeutic drug monitoring, to optimize CsA dosing in transplant recipients.
Création de la notice
10/03/2008 10:53
Dernière modification de la notice
20/08/2019 12:54
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