A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient

作者：Chang Jeremy B; Quinnies Kayla M; Realubit Ronald; Karan Charles; Rand Jacob H; Tatonetti Nicholas P^*

来源：Scientific Reports, 2016, 6(1): 29387.

DOI：10.1038/srep29387

A central challenge in designing and administering effective anticoagulants is achieving the proper therapeutic window and dosage for each patient. The Hill coefficient, n(H), which measures the steepness of a dose-response relationship, may be a useful gauge of this therapeutic 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.

• 出版日期2016-7-21