In vivo models for the evaluation of antithrombotics and thrombolytics.
The development and application of animal models of thrombosis have played a crucial role in the discovery and validation of novel drug targets and the selection of new agents for clinical evaluation, and have informed dosing and safety information for clinical trials. These models also provide valuable information about the mechanisms of action/interaction of new antithrombotic agents. Small and large animal models of thrombosis and their role in the discovery and development of novel agents are described. Methods and major issues regarding the use of animal models of thrombosis, such as positive controls, appropriate pharmacodynamic markers of activity, safety evaluation, species specificity, and pharmacokinetics, are highlighted. Finally, the use of genetic models of thrombosis/hemostasis and how these models have aided in the development of therapies that are presently being evaluated clinically are presented.
Mousa
Shaker A
SA
Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA.
D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D002712:Chlorides / Q000009:adverse effects; D003251:Constriction, Pathologic / Q000150:complications; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004560:Electricity / Q000009:adverse effects; D005260:Female; D005290:Ferric Compounds / Q000009:adverse effects; D005343:Fibrinolytic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005547:Foreign Bodies / Q000150:complications; D006402:Hematologic Diseases / Q000188:drug therapy / Q000209:etiology; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007834:Lasers / Q000009:adverse effects; D008297:Male; D051379:Mice; D008957:Models, Genetic; D055668:Photochemical Processes; D011817:Rabbits; D051381:Rats; D013314:Stress, Mechanical; D013917:Thrombin / Q000009:adverse effects; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000235:genetics
D002712:Chlorides; D005290:Ferric Compounds; D005343:Fibrinolytic Agents; D013917:Thrombin; C024555:ferric chloride