title: Population Pharmacokinetic and Pharmacodynamic Modeling Analysis of GCC-4401C, a Novel Direct Factor Xa Inhibitor, in Healthy Volunteers.
abstract: GCC-4401C, an orally active direct factor Xa inhibitor that is similar to rivaroxaban, is currently under development for venous thromboembolic disease (VTE). The purpose of this study was to characterize the pharmacokinetics (PKs) and pharmacodynamics (PDs) of GCC-4401C by population modeling analysis and to predict proper dosage regimens compared to rivaroxaban using data from two phase I clinical studies. Plasma GCC-4401C concentrations over time were best described by a two-compartment linear model and body weight was associated with central volume of distribution. Relevant PD markers generally changed in a dose-dependent manner and were described well with sigmoid, simple maximum effect, or linear models. GCC-4401C was absorbed more rapidly than rivaroxaban. Comparisons based on simulations of PD marker changes over time suggest that 20 mg and 40 mg of GCC-4401C administered under fasted status are comparable to 10 mg and 20 mg of rivaroxaban under fed status.
authors: Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Ulsan University College of Medicine, Republic of Korea.
authors: H Y
authors: HY
authors: Choi
authors: Research Center, Green Cross Corporation, Yongin, Republic of Korea.
authors: S
authors: S
authors: Choi
authors: Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Ulsan University College of Medicine, Republic of Korea.
authors: Y H
authors: YH
authors: Kim
authors: Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, Ulsan University College of Medicine, Republic of Korea. mdhslim@gmail.com.
authors: H S
authors: HS
authors: Lim
mesh_terms: D000328:Adult; D017321:Clinical Trials, Phase I as Topic; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008954:Models, Biological; D016032:Randomized Controlled Trials as Topic; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D065427:Factor Xa Inhibitors; C100738:GCC-AP 0341; D014230:Triazoles