Quantification of unbound concentration of ticagrelor in plasma as a proof of mechanism biomarker of the reversal agent, MEDI2452.

ABSTRACT: Ticagrelor, a P2Y12 antagonist, is approved for prevention of thromboembolic events. MEDI2452 is a potential reversal agent for ticagrelor and ticagrelor active metabolite (TAM). The total plasma exposure of ticagrelor and TAM in patients are roughly 0.5-1 and 0.2-0.5 μmol/L, respectively. Both have similar high potency vs. P2Y12 (Ki 2 nmol/L) but are plasma protein-bound to 99.8% and only the 0.2% free fraction is able to inhibit the P2Y12 receptor. Thus, for unbound concentration measurements to be a proof of mechanism biomarker for MEDI2452 a very high sensitivity is required. Using established techniques as equilibrium dialysis and LC-MS/MS, made it possible to evaluate the efficacy of the reversal agent by measuring reduction of unbound concentration of ticagrelor in the presence of M

SUBMITTER: Sandinge AS 

PROVIDER: S-EPMC6062093 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature