Pharmacokinetics of BAY 59-7939--an oral, direct Factor Xa inhibitor--in rats and dogs.

摘要: The pharmacokinetics of BAY 59-7939 - a novel, oral, direct Factor Xa inhibitor were investigated in rats and dogs support preclinical safety studies clinical development. was rapidly absorbed after oral dosing, with an absolute bioavailability 57-66% rats, 60-86% dogs. Plasma linear across the dose range (1-10 mg kg(-1) 0.3-3 dogs). clearance low: 0.4 l h(-1) 0.3 dogs; volume distribution (V(ss)) moderate: elimination half-life administration short both species (0.9-2.3 h). Whole-body autoradiography showed moderate tissue affinity. No retention or small enrichments 59-7939-related radioactivity observed. plasma-protein binding high, dependent fully reversible. excreted dogs, not irreversibly retained. A dual mode excretion (biliary/faecal renal) In summary, had favourable, predictable pharmacokinetic profile, high route excretion.