title: Pharmacodynamic evaluation of clopidogrel plus PA32540: the Spaced PA32540 With Clopidogrel Interaction Gauging (SPACING) study.
abstract: PA32540 combines 325 mg enteric-coated (EC) aspirin (ASA) with 40 mg immediate-release omeprazole; its influence on the antiplatelet effect of clopidogrel (C) is unknown. In this randomized, open-label study, subjects (n = 30) were treated with (i) 300 mg C + 325 mg ECASA followed by 75 mg C + 325 mg ECASA on days 2-7, (ii) 300 mg C + PA32540 followed by 75 mg C + PA32540 on days 2-7, or (iii) PA32540 in the morning + 300 mg C 10 h later on day 1 and PA32540 in the morning + 75 mg C 10 h later on days 2-7. We analyzed the noninferiority of PA32540 relative to ECASA, as defined by the upper bound of the 95% confidence interval ≤10% for the difference in least-square means of platelet inhibition between the treatments. As compared to ECASA+C, synchronous treatment of PA32540+C was not noninferior, whereas the spacing strategy of PA32540+C was noninferior. Spacing the administration of PA32540 and clopidogrel lessens the interaction observed with synchronous administration; PA32540 administration with clopidogrel may be associated with a different antiplatelet profile.
authors: Sinai Center for Thrombosis Research, Baltimore, Maryland, USA. pgurbel@lifebridgehealth.org
authors: P A
authors: PA
authors: Gurbel
authors: K P
authors: KP
authors: Bliden
authors: J
authors: J
authors: Fort
authors: Y
authors: Y
authors: Zhang
authors: J R
authors: JR
authors: Plachetka
authors: M
authors: M
authors: Antonino
authors: M
authors: M
authors: Gesheff
authors: U S
authors: US
authors: Tantry
mesh_terms: D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D000077144:Clopidogrel; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D013608:Tablets, Enteric-Coated; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000897:Anti-Ulcer Agents; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D013608:Tablets, Enteric-Coated; D000077144:Clopidogrel; D009853:Omeprazole; D013988:Ticlopidine; D001241:Aspirin