Evaluation of drug-drug interaction potential between omecamtiv mecarbil and rosuvastatin, a BCRP substrate, with a clinical study in healthy subjects and using a physiologically-based pharmacokinetic model.

ABSTRACT: Omecamtiv mecarbil (OM) is a novel cardiac myosin activator in development for the treatment of heart failure. In vitro, OM is an inhibitor of BCRP. Rosuvastatin, a BCRP substrate, is one of the most commonly prescribed medications in patients with heart failure. The potential for a pharmacokinetic (PK) drug-drug interaction (DDI) was investigated, specifically to determine whether a single 50 mg dose of OM would impact the PKs of a single 10 mg dose of rosuvastatin in an open-label study in 14 healthy subjects. The ratios of the geometric least-square means (90% confidence intervals [CIs]) of rosuvastatin co-administered with OM compared to rosuvastatin alone were 127.1% (90% CI 113.8-141.9), 132.8% (90% CI 120.7-146.1), and 154.2% (90% CI 132.8-179.1) for area under the plasma-concentrat

SUBMITTER: Trivedi A 

PROVIDER: S-EPMC8604240 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature