Journal article

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



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 ..

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