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Pharmacodynamic Evaluation of Clopidogrel Plus PA32540: The Spaced PA32540 With Clopidogrel Interaction Gauging (SPACING) Study
Author(s) -
Gurbel P A,
Bliden K P,
Fort J,
Zhang Y,
Plachetka J R,
Antonino M,
Gesheff M,
Tantry U S
Publication year - 2011
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2011.201
Subject(s) - clopidogrel , morning , pharmacodynamics , medicine , pharmacology , confidence interval , aspirin , drug interaction , omeprazole , anesthesia , crossover study , pharmacokinetics , placebo , alternative medicine , pathology
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. Clinical Pharmacology & Therapeutics (2011); 90 6, 860–866. doi: 10.1038/clpt.2011.201