A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient
| Autor: | Nicholas P. Tatonetti, Jacob H. Rand, Ronald Realubit, Charles Karan, Jeremy B. Chang, Kayla M. Quinnies |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Blood Platelets
Administration Oral 030204 cardiovascular system & hematology Pharmacology Fondaparinux Arginine Argatroban Article 03 medical and health sciences Inhibitory Concentration 50 Plasma 0302 clinical medicine Pharmacokinetics Polysaccharides medicine Inhibitory concentration 50 Humans Fluorometry Blood Coagulation Platelet-poor plasma Therapeutic window Sulfonamides Multidisciplinary Dose-Response Relationship Drug business.industry Thrombin Anticoagulants Confidence interval Dose–response relationship Pipecolic Acids business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep29387 |
| Popis: | A central challenge in designing and administering effective anticoagulants is achieving the proper therapeutic window and dosage for each patient. The Hill coefficient, nH, which measures the steepness of a dose-response relationship, may be a useful gauge of this therapeutic window. We sought to measure the Hill coefficient of available anticoagulants to gain insight into their therapeutic windows. We used a simple fluorometric in vitro assay to determine clotting activity in platelet poor plasma after exposure to various concentrations of anticoagulants. The Hill coefficient for argatroban was the lowest, at 1.7 ± 0.2 (95% confidence interval, CI), and the Hill coefficient for fondaparinux was the highest, at 4.5 ± 1.3 (95% CI). Thus, doubling the dose of fondaparinux from its IC50 would decrease coagulation activity by nearly a half, whereas doubling the dose of argatroban from its IC50 would decrease coagulation activity by merely one quarter. These results show a significant variation among the Hill coefficients, suggesting a similar variation in therapeutic windows among anticoagulants in our assay. |
| Databáze: | OpenAIRE |
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