Edoxaban Exposure-Response Analysis and Clinical Utility Index Assessment in Patients With Symptomatic Deep-Vein Thrombosis or Pulmonary Embolism
2016 (English)In: CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY, ISSN 2163-8306, Vol. 5, no 4, 222-232 p.Article in journal (Refereed) Published
Edoxaban exposure-response relationships from the phase III study evaluating edoxaban for prevention and treatment of venous thromboembolism (VTE) in patients with acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE) were assessed by parametric time-to-event analysis. Statistical significant exposure-response relationships were recurrent VTE with hazard ratio (HR) based on average edoxaban concentration at steady state (C-av) (HRCav) 50.98 (i.e., change in the HR with every 1 ng/mL increase of C-av); the composite of recurrent DVT and nonfatal PE with HRC(av)50.99; and the composite of recurrent DVT, nonfatal PE, and all-cause mortality HRC(av)50.98, and all death using maximal edoxaban concentration (C-max) with HR (C-max) 50.99. No statistical significant exposure-response relationships were found for clinically relevant bleeding or major adverse cardiovascular event. Results support the recommendation of once-daily edoxaban 60 mg, and a reduced 30 mg dose in patients with moderate renal impairment, body weight <= 60 kg, or use of P-glycoprotein inhibitors verapamil or quinidine.
Place, publisher, year, edition, pages
2016. Vol. 5, no 4, 222-232 p.
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:uu:diva-303402DOI: 10.1002/psp4.12077ISI: 000381564500007PubMedID: 27299709OAI: oai:DiVA.org:uu-303402DiVA: diva2:971754