BACKGROUND: tacrolimus and everolimus are immunosuppressive drugs metabolized by enzymes of the CYP3A subfamily. A common variant of the CYP3A5 gene, CYP3A5*3, results in strongly decreased CYP3A5 activity and has been shown to influence Tacrolimus blood concentrations, but its role for the pharmacogenetics of Everolimus remains unclear. Aim of the study was to examine the role of CYP3A5*3 variant in tacrolimus and everolimus dose and drug levels after heart transplantation. METHODS: The present study comprised 15 patients with Tacrolimus and 30 patients with Everolimus-based maintenance therapy after heart transplantation. CYP3A5 genotypes were determined and correlated with clinical data. RESULTS: In the Tacrolimus group, 13 subjects were CYP3A5 non-expressors (*3/*3 genotype) and two were heterozygous expressors (*1/*3 genotype). Average Tacrolimus dose was significantly higher in subjects expressing CYP3A5 compared to non-expressors. Tacrolimus levels were not significantly different at any point of time. In the Everolimus group, 27 subjects were CYP3A5 non-expressors (*3/*3 genotype) and three were heterozygous expressors (*1/*3). Neither Everolimus dose nor levels were significantly different between CYP3A5 expressors and non-expressors at any point of time. DISCUSSION: We conclude that in adult patients after heart transplantation, CYP3A5 genotypes have a strong influence on Tacrolimus, but not Everolimus dose requirement.
BACKGROUND:tacrolimus and everolimus are immunosuppressive drugs metabolized by enzymes of the CYP3A subfamily. A common variant of the CYP3A5 gene, CYP3A5*3, results in strongly decreased CYP3A5 activity and has been shown to influence Tacrolimus blood concentrations, but its role for the pharmacogenetics of Everolimus remains unclear. Aim of the study was to examine the role of CYP3A5*3 variant in tacrolimus and everolimus dose and drug levels after heart transplantation. METHODS: The present study comprised 15 patients with Tacrolimus and 30 patients with Everolimus-based maintenance therapy after heart transplantation. CYP3A5 genotypes were determined and correlated with clinical data. RESULTS: In the Tacrolimus group, 13 subjects were CYP3A5 non-expressors (*3/*3 genotype) and two were heterozygous expressors (*1/*3 genotype). Average Tacrolimus dose was significantly higher in subjects expressing CYP3A5 compared to non-expressors. Tacrolimus levels were not significantly different at any point of time. In the Everolimus group, 27 subjects were CYP3A5 non-expressors (*3/*3 genotype) and three were heterozygous expressors (*1/*3). Neither Everolimus dose nor levels were significantly different between CYP3A5 expressors and non-expressors at any point of time. DISCUSSION: We conclude that in adult patients after heart transplantation, CYP3A5 genotypes have a strong influence on Tacrolimus, but not Everolimus dose requirement.
Authors: Violette Gijsen; Seema Mital; Ron H van Schaik; Offie P Soldin; Steven J Soldin; Ilse P van der Heiden; Irena Nulman; Gideon Koren; Saskia N de Wildt Journal: J Heart Lung Transplant Date: 2011-09-17 Impact factor: 10.247
Authors: Dirk Jan A R Moes; Rogier R Press; Jan den Hartigh; Tahar van der Straaten; Johan W de Fijter; Henk-Jan Guchelaar Journal: Clin Pharmacokinet Date: 2012-07-01 Impact factor: 6.447
Authors: Dennis A Hesselink; Rachida Bouamar; Laure Elens; Ron H N van Schaik; Teun van Gelder Journal: Clin Pharmacokinet Date: 2014-02 Impact factor: 6.447
Authors: D J A R Moes; J J Swen; J den Hartigh; T van der Straaten; J J Homan van der Heide; J S Sanders; F J Bemelman; J W de Fijter; H J Guchelaar Journal: CPT Pharmacometrics Syst Pharmacol Date: 2014-02-12