BACKGROUND: The high inter-individual variability of inhibition of platelet function by @entity1397 is mostly explained by high variability in its transformation to active metabolite ( @entity5380 ). OBJECTIVE: We investigated the relations between pharmacokinetics and pharmacodynamics of @entity5380 comparing two methods of platelet function. METHODS: We enrolled 14 @entity1 undergoing percutaneous coronary interventions for NSTE-ACS or inducible @entity741 . Plasma concentrations of @entity1397 and @entity5380 , phosphorylation of @entity19319 ( @entity19319 ), expressed as platelet reactivity index (PRI), and whole-blood @entity1423 (Multiple Electrode Aggregometer, @entity17585 ) were measured before and after 600 mg @entity1397 loading dose (9 time points) and before and after 75 mg maintenance doses at days 2, 7 and 30. RESULTS: Plasma concentrations of @entity1397 and @entity5380 were highly variable. @entity5380 reached maximal concentration (Cmax ) (median: 110.8 nmol/L; range: 41.9-484.8) 0.5-2h after the loading dose. A sigmoid dose-response curve defined the relations between @entity5380 Cmax and PRI from 3h to 24h (IC50 : 459.6 nmol/L, 95% CI: 453.4-465.7, R(2) =0.82). PRI was unchanged from baseline in @entity1 with the lowest @entity5380 Cmax (<83 nmol/L, n=7), indicating low sensitivity of @entity19319 . PRI values were also predicted by @entity5380 Cmax at days 2, 7 and 30. @entity1423 measured by MEA did not show significant relations either with PRI or with @entity5380 pharmacokinetics at any time point. CONCLUSIONS: After 600 mg @entity1397 , @entity19319 , but not whole-blood @entity1423 measured by MEA, is almost entirely predicted by @entity5380 Cmax . @entity19319 could be useful in studies aiming at investigating relations between @entity5380 bioavailability and clinical events. This article is protected by copyright. All rights reserved.

Relationship between pharmacokinetics and pharmacodynamics of XXXX in @entity1 undergoing percutaneous coronary intervention: comparison between vasodilator-stimulated phosphoprotein phosphorylation assay and multiple electrode aggregometry.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity1423 :: ('MESH:D001791', 'Disease') :: ['platelet aggregation', 'Platelet aggregation'] @entity1397 :: ('MESH:C055162', 'Chemical') :: ['clopidogrel'] @entity17585 :: ('CHEBI:16000', 'Chemical') :: ['MEA'] @entity5380 :: ('MESH:D020786', 'Disease') :: ['CAM'] @entity741 :: ('MESH:D017202', 'Disease') :: ['myocardial ischemia'] @entity19319 :: ('7408', 'Gene') :: ['VASP-P', 'vasodilator stimulated phosphoprotein']
@entity1397 :: (MESH:C055162,Chemical) :: ['clopidogrel']
