title: Pharmacokinetics, pharmacodynamics and food effect of LB30870, a novel direct thrombin inhibitor, after single oral doses in healthy men.
abstract: 1. The safety, tolerability, pharmacokinetics, pharmacodynamics, and food effect of LB30870, a new selective thrombin inhibitor, were studied in 16 healthy men. 2. A double-blind, placebo-controlled single ascending dose study was done at oral doses of 5, 15, 30, 60, 120, and 240 mg under fasting conditions. An open, randomized, balanced cross-over food effect study was done at 60 mg dose. Plasma and urinary concentrations were measured up to 48 h post-dose. Coagulation and thrombin activity markers were measured at selected time points. 3. Cmax of LB30870 was at 1.3-3.0 h post-dose with a mean apparent terminal half-life (t1/2) of 2.8-4.1 h. AUC after doses above 15 mg appeared greater than dose-proportional. In fed state, AUC showed 80% reduction relative to fasting condition. 4. At doses 60 and 120 mg, peak activated partial thromboplastin time (aPTT) increased by 1.5- and 2-fold, respectively, from baseline. The aPTT and international normalized ratio (INR) were concentration-dependent, with less within-individual variability than ecarin clotting time (ECT), prothrombin time (PT), or thrombin time (TT). 5. Single oral doses of LB30870 up to 240 mg were well tolerated. The food effect must be overcome if LB30870 is to be used as an oral anti-coagulant.
authors: Drug Metabolism & Pharmacokinetics, LG Life Sciences , Daejeon , Korea .
authors: John
authors: J
authors: Kim
authors: Sung-Hack
authors: SH
authors: Lee
authors: Malcolm
authors: M
authors: Boyce
authors: Steve
authors: S
authors: Warrington
authors: Kwan Hyung
authors: KH
authors: Cho
authors: Suk Kyoon
authors: SK
authors: Yoon
authors: Hee Dong
authors: HD
authors: Park
authors: Aeri
authors: A
authors: Kim
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000578:Amidines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000925:Anticoagulants / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000991:Antithrombins / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D054316:Biomarkers, Pharmacological / Q000097:blood / Q000652:urine; D001777:Blood Coagulation / Q000187:drug effects*; D018592:Cross-Over Studies; D004151:Dipeptides / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005463:Fluoroacetates; D018565:Food-Drug Interactions / Q000502:physiology*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000578:Amidines; D000925:Anticoagulants; D000991:Antithrombins; D054316:Biomarkers, Pharmacological; D004151:Dipeptides; D005463:Fluoroacetates; C476981:N-aminosulfonyldiphenylalanyl-prolyl-((4-amidinophenyl)methyl)amide
keywords: Anti-coagulant; coagulation markers; dose-proportionality