Evaluation of a New Blood Coagulation Factor Xa Inhibitor, KFA-1411, as an Anticoagulant in a Cynomolgus Monkey Hemodialysis Model: Parameters Suitable for Monitoring Anticoagulant Activities
| Autor: | Kiyoto Hara, Masami Kojima, Satoshi Akahane, Takashi Koizumi, Toshiki Honma, Yuji Hoyano, Masahiko Uchida, Masuo Akahane |
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| Rok vydání: | 2003 |
| Předmět: |
Prothrombin time
medicine.drug_mechanism_of_action medicine.diagnostic_test medicine.drug_class business.industry Health Toxicology and Mutagenesis medicine.medical_treatment Extracorporeal circulation Anticoagulant Factor Xa Inhibitor Heparin Toxicology Clotting time Anesthesia medicine Hemodialysis business medicine.drug Partial thromboplastin time |
| Zdroj: | Journal of Health Science. 49:368-378 |
| ISSN: | 1347-5207 1344-9702 |
| Popis: | A Cynomolgus monkey hemodialysis model was used to evaluate the efficacy of a new factor Xa (FXa) inhibitor as an anticoagulant for hemodialysis. We tested the selective FXa inhibitor KFA-1411, using doses of 0.15 mg/ kg/hr, 0.3 mg/kg/hr, and 0.6 mg/kg/hr by continuous infusion in combination with a single loading-dose at the start. As a reference control, dalteparin, which is a low-molecular-weight heparin, was used at a dose of 20 IU/kg/hr plus 30 IU/kg single loading. As a monitoring method for KFA-1411, clotting time was measured in blood samples obtained from the body (systemic) and from the extracorporeal circulation (in-circuit). At KFA-1411 doses of 0.3 mg/ kg/hr and 0.6 mg/kg/hr hemodialysis was maintained with essentially no change in the intra-bloodline pressure in the extracorporeal circulation. With dalteparin, the pressure increased almost to the upper limit (set at 250 mmHg). The clot-deposition score measured, after testoration of normal circulation, in the dialyzer and air-trap chamber in the extracorporeal circulation was improved in a dose‐dependent manner in the KFA-1411 groups. There were no large differences between humans and Cynomolgus monkeys in the in vitro plasma anticoagulant activities of KFA1411 and dalteparin. These results indicate that this selective FXa inhibitor could be used as an anticoagulant for hemodialysis. Both activated partial thromboplastin time (APTT) and prothrombin time (PT) can be used to monitor the anticoagulant activity in the extracorporeal circulation, and a drug dose that has sufficient anticoagulant efficacy for hemodialysis will prolong in-circuit-APTT about 2 times and in-circuit-PT about 3 times compared to normal. |
| Databáze: | OpenAIRE |
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