Influence of CYP3A5 genetic variation on everolimus maintenance dosing after cardiac transplantation
Dorothea Lesche, Vilborg Sigurdardottir, Raschid Setoud, Lars Englberger, Georg M Fiedler, Carlo R Largiader, Paul Mohacsi, Johanna Sistonen
CLINICAL TRANSPLANTATION | WILEY | Published : 2015
BACKGROUND: Everolimus (ERL) has become an alternative to calcineurin inhibitors (CNIs) due to its renal-sparing properties, especially in heart transplant (HTx) recipients with kidney dysfunction. However, ERL dosing is challenging due to its narrow therapeutic window combined with high interindividual pharmacokinetic variability. Our aim was to evaluate the effect of clinical and genetic factors on ERL dosing in a pilot cohort of 37 HTx recipients. METHODS: Variants in CYP3A5, CYP3A4, CYP2C8, POR, NR1I2, and ABCB1 were genotyped, and clinical data were retrieved from patient charts. RESULTS: While ERL trough concentration (C0 ) was within the targeted range for most patients, over 30-fold ..View full abstract
Awarded by Swiss National Science Foundation
This study was supported by the Foundation for Pathobiochemistry and Molecular Diagnostics of the German Society of Clinical Chemistry and Laboratory Medicine (DGKL), the K. Huber-Steiner Foundation, and the Swiss National Science Foundation (grants 119839 and 138285).