A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • July 21, 2016

Research

keywords

  • Anticoagulants
  • Blood Platelets
  • Pipecolic Acids
  • Polysaccharides

Identity

PubMed Central ID

  • PMC4954953

Scopus Document Identifier

  • 84979247388

Digital Object Identifier (DOI)

  • 10.1038/srep29387

PubMed ID

  • 27439480

Additional Document Info

volume

  • 6