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

Jeremy B. Chang, Kayla M. Quinnies, Ronald Realubit, Charles Karan, Jacob H. Rand, Nicholas P. Tatonetti

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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 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.

Original languageEnglish
Article number29387
JournalScientific Reports
Volume6
DOIs
StatePublished - 21 Jul 2016
Externally publishedYes

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