Premium
Pharmacokinetics of Otamixaban, a Direct Factor Xa Inhibitor, in Healthy Male Subjects: Pharmacokinetic Model Development for Phase 2/3 Simulation of Exposure
Author(s) -
Paccaly Anne,
Frick Annke,
Rohatagi Shashank,
Liu Jingli,
Shukla Umesh,
Rosenburg Ronald,
Hinder Markus,
Jensen Bradford K.
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005281817
Subject(s) - pharmacokinetics , volume of distribution , medicine , bolus (digestion) , pharmacology , intravenous bolus , plasma clearance , distribution (mathematics) , elimination rate constant , mathematics , mathematical analysis
The pharmacokinetics of otamixaban was investigated in healthy male subjects over a wide range of intravenous doses, with duration of administration varying between 1‐minute infusions (bolus dose) and 24‐hour infusions, using noncompartmental and multicompartmental methods. A global compartmental analysis (2 and 3 compartments) generated a single set of pharmacokinetic parameters, regardless of infusion rate and duration, and took into account the 30% decrease in clearance and volume of distribution observed over the dose range. The 2‐compartment model was retained to predict bolus plus 3‐hour‐infusion doses of otamixaban for future phase 2/3 studies. Otamixaban exhibited in healthy subjects several interesting pharmacokinetic features in view of its potential therapeutic use in coronary thrombosis: a rapid plasma distribution and elimination, a well‐described dose‐exposure relationship, a low intersubject variability in plasma exposure, and a mixed renal and biliary excretion with constant renal clearance.