Functional in vitro characterization of SLCO1B1 variants and simulation of the clinical pharmacokinetic impact of impaired OATP1B1 function.
Wilma Kiander, Noora Sjöstedt, R. Manninen, Liina Jaakkonen, Kati-Sisko Vellonen, Mikko Neuvonen, Mikko Niemi, Seppo Auriola, Heidi Kidron
Abstract
. Based on pharmacokinetic simulations, doses of 30 mg (with 50% OATP1B1 function) and 20 mg (with 0% OATP1B1 function) result in plasma exposure similar to 40 mg dose (with 100% OATP1B1 function). Therefore dose reductions might be considered to avoid increased plasma exposure caused by function-impairing OATP1B1 genetic variants, such as R57Q.
Topics & Concepts
SLCO1B1RosuvastatinPharmacokineticsPharmacologyChemistryOrganic anion-transporting polypeptideOrganic anion transporter 1TransporterPharmacogeneticsBiologyBiochemistryGenotypeGeneDrug Transport and Resistance MechanismsLipoproteins and Cardiovascular HealthPharmacogenetics and Drug Metabolism