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Spaced administration of PA32540 and clopidogrel results in greater platelet inhibition than synchronous administration of enteric-coated aspirin and enteric-coated omeprazole and clopidogrel.

Publication ,  Journal Article
Gurbel, PA; Bliden, KP; Fort, JG; Jeong, Y-H; Shuldiner, A; Chai, S; Gesheff, T; Antonino, M; Gesheff, M; Zhang, Y; Tantry, US
Published in: Am Heart J
February 2013

BACKGROUND: A common regimen for patients requiring dual-antiplatelet therapy who are at risk for gastrointestinal complications is the synchronous administration of enteric-coated (EC) aspirin, a proton pump inhibitor, and clopidogrel, although proton pump inhibitors have the potential for pharmacodynamic interaction with clopidogrel. Spaced administration of a clopidogrel and a single-tablet formulation of aspirin and immediate-release omeprazole (PA32540) was considered as an alternative that might reduce this potential pharmacodynamic interaction. METHODS AND RESULTS: A randomized, open-label, crossover study was conducted in healthy subjects (n = 30). Two 7-day treatments were separated by 14-day washout periods: (a) PA32540 + clopidogrel (300 mg loading/75 mg maintenance) 10 hours later and (b) synchronous dosing of clopidogrel + EC aspirin (81 mg) + EC omeprazole (40 mg). The primary end point was the inhibition of platelet aggregation (20 μM adenosine diphosphate, maximal extent) after 7 days. CYP2C19 and ABCB1 genotypes were determined. Inhibition of platelet aggregation was greater with spaced PA32540 + clopidogrel therapy vs synchronous clopidogrel + EC aspirin + EC omeprazole therapy (P = .004). There was no difference in day 7 arachidonic acid-induced aggregation. The effect of spacing on pharmacodynamics was independent of genotype. CONCLUSIONS: PA32540 and clopidogrel spaced 10 hours apart had greater antiplatelet effects than did synchronously administered EC aspirin (81 mg), clopidogrel (75 mg), and EC omeprazole in healthy volunteers. These finding are directly relevant to the treatment for patients with high gastrointestinal risk who require dual-antiplatelet therapy and gastroprotection.

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Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

February 2013

Volume

165

Issue

2

Start / End Page

176 / 182

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Ticlopidine
  • Tablets, Enteric-Coated
  • Platelet Aggregation Inhibitors
  • Platelet Aggregation
  • Omeprazole
  • Middle Aged
  • Humans
  • Gastrointestinal Diseases
  • Follow-Up Studies
 

Citation

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Gurbel, P. A., Bliden, K. P., Fort, J. G., Jeong, Y.-H., Shuldiner, A., Chai, S., … Tantry, U. S. (2013). Spaced administration of PA32540 and clopidogrel results in greater platelet inhibition than synchronous administration of enteric-coated aspirin and enteric-coated omeprazole and clopidogrel. Am Heart J, 165(2), 176–182. https://doi.org/10.1016/j.ahj.2012.07.032
Gurbel, Paul A., Kevin P. Bliden, John G. Fort, Young-Hoon Jeong, Alan Shuldiner, Sumbul Chai, Tania Gesheff, et al. “Spaced administration of PA32540 and clopidogrel results in greater platelet inhibition than synchronous administration of enteric-coated aspirin and enteric-coated omeprazole and clopidogrel.Am Heart J 165, no. 2 (February 2013): 176–82. https://doi.org/10.1016/j.ahj.2012.07.032.
Gurbel PA, Bliden KP, Fort JG, Jeong Y-H, Shuldiner A, Chai S, Gesheff T, Antonino M, Gesheff M, Zhang Y, Tantry US. Spaced administration of PA32540 and clopidogrel results in greater platelet inhibition than synchronous administration of enteric-coated aspirin and enteric-coated omeprazole and clopidogrel. Am Heart J. 2013 Feb;165(2):176–182.
Journal cover image

Published In

Am Heart J

DOI

EISSN

1097-6744

Publication Date

February 2013

Volume

165

Issue

2

Start / End Page

176 / 182

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Ticlopidine
  • Tablets, Enteric-Coated
  • Platelet Aggregation Inhibitors
  • Platelet Aggregation
  • Omeprazole
  • Middle Aged
  • Humans
  • Gastrointestinal Diseases
  • Follow-Up Studies