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46 Urinary prostanoid metabolites in healthy volunteers taking prasugrel and aspirin
  1. P D M Leadbeater1,
  2. N S Kirkby1,2,
  3. S Thomas3,4,
  4. A-R Dhanji2,
  5. A T Tucker5,
  6. G L Milne3,4,
  7. J A Mitchell1,
  8. T D Warner2
  1. 1Cardiothoracic Pharmacology, NHLI, Imperial College London, UK
  2. 2The William Harvey Research Institute, Barts & the London School of Medicine & Dentistry, Barts, UK
  3. 3Department of Pharmacology, Vanderbilt University, Nashville, USA
  4. 4Department of Medicine, Vanderbilt University, Nashville, USA
  5. 5The Ernest D Cooke Clinical Microvascular Unit, St Bartholomew's Hospital, London, UK

Abstract

This study evaluated the effect of prasugrel alone, and in combination with low and high dose aspirin, on urinary metabolites of thromboxane A2 (TXA2) and prostaglandin I2 (PGI2), TX-M and PGI-M, respectively. 9 healthy males, aged 18–40, were enrolled in the 21-day study. Prasugrel was loaded at 60 mg on day 1 and maintained at 10 mg once daily until day 21. At day 8 aspirin 75 mg o.d. was introduced and the dose increased to 300 mg o.d. on day 15. On days 0, 7, 14 and 21 urine samples were obtained and TX-M and PGI-M assayed by mass spectrometry. Platelet aggregation to a TXA2-mimetic (U46619) was also determined at each time point. Data are presented as ng of urinary metabolite per mg creatine (mean±SEM). Data were analysed by one-way ANOVA with Bonferroni's post-test. Prasugrel alone did not reduce either TX-M (day 7, 0.24±0.02 ng per mg creatine; day 0, 0.28±0.04) or PGI-M (day 7, 0.15±0.03; day 0, 0.15±0.04), although both metabolites were reduced by the addition of low dose aspirin (day 14: TX-M, 0.09±0.01; PGI-M, 0.07±0.01; p<0.01 vs day 0). There were no further effects with the higher aspirin dose (p>0.05). Platelet aggregation to U46619 was largely inhibited by prasugrel, with no further effect of aspirin. Prasugrel alone preserves urinary PGI2 metabolites while inhibiting TXA2-driven platelet aggregation. Addition of aspirin reduces the excreted levels of metabolites of both TXA2 and vasoprotective PGI2.

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