Drug evaluation: the directly activated Factor Xa inhibitor otamixaban.
Otamixaban, under development by sanofi-aventis, is a directly activated Factor X (FXa) inhibitor that is currently in phase IIb clinical trials for acute coronary syndrome and myocardial infarction. Preclinical studies with otamixaban demonstrated high selectivity of the compound for FXa. Otamixaban effectively inhibited thrombin generation without interfering with existing thrombin activity. Intravenously administered otamixaban was well tolerated in both male and female patients, independent of age. Otamixaban exhibited a well-described dose-exposure relationship, a low inter-patient variability in plasma exposure, and was both rapidly distributed in the plasma and quickly eliminated. The rapid decrease in otamixaban plasma concentrations following the termination of an infusion is an advantage over other FXa inhibitors that have longer half-lives. Otamixaban exhibited an improved pharmacodynamic profile over conventional anticoagulant therapies such as heparin. During clinical trials with otamixaban, no major drug interactions were observed with agents that were likely to be used in combination therapy. Otamixaban is a promising agent that merits further consideration for clinical trials in patients with coronary thrombosis.
Nutescu
Edith A
EA
Antithrombosis Center, Department of Pharmacy Practice, College of Pharmacy, The University of Illinois at Chicago, Chicago, IL 60612-7230, USA. enutescu@uic.edu
Pater
Karen
K
D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D017322:Clinical Trials, Phase II as Topic; D003328:Coronary Thrombosis / Q000188:drug therapy; D003497:Cyclic N-Oxides / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D065427:Factor Xa Inhibitors; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy; D011725:Pyridines / Q000009:adverse effects / Q000138:chemical synthesis / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D013329:Structure-Activity Relationship
D000925:Anticoagulants; D003497:Cyclic N-Oxides; D065427:Factor Xa Inhibitors; D011725:Pyridines; C435830:otamixaban