An Ex Vivo Study to Evaluate the Effect of Tegaserod on Platelet Activation and Aggregation.

Journal of Cardiovascular Pharmacology and Therapeutics
Paul A GurbelUdaya Tantry

Abstract

Tegaserod, an orally active, potent 5-hydroxytryptamine-4 serotonin receptor agonist, was previously indicated for irritable bowel syndrome but was voluntarily withdrawn due to potential cardiovascular side effects. In vitro studies suggested that tegaserod increased platelet aggregation, but these results were not reproduced or were inconclusive. We sought to assess ex vivo effects of tegaserod on platelet aggregation. In this double-blind, placebo-controlled, crossover study, we randomized a majority of healthy patients with no history of cardiovascular risk factors (n = 21) to receive tegaserod or matching placebo for 7 + 2 days followed by a 7- to 10-day washout period, and then patients were crossed over to the other study drug for the next 7 + 2 days. Unstimulated and agonist-stimulated platelet aggregation; P-selectin expression; serum thromboxane (Tx)B2 and urinary 11-dehydro (11-dh) TxB2; and tegaserod and M29.0 concentrations were serially assessed. There was no significant difference in percentage change in unstimulated or adenosine diphosphate (ADP)- and ADP + serotonin-, collagen- and thrombin receptor activating peptide-induced maximum platelet aggregation and in platelet P-selectin expression in the presence of t...Continue Reading

References

Feb 24, 2001·Alimentary Pharmacology & Therapeutics·M Camilleri
Nov 4, 2004·Alimentary Pharmacology & Therapeutics·J F Johanson
Aug 30, 2005·Journal of Emergency Nursing : JEN : Official Publication of the Emergency Department Nurses Association·Lisa DuganJoy Corriher
Nov 16, 2005·Journal of the American College of Cardiology·Paul A GurbelUdaya S Tantry
Jul 16, 2009·Journal of Cardiovascular Pharmacology and Therapeutics·Jeffrey L AndersonJohn F Carlquist
Oct 3, 2009·American Journal of Therapeutics·Victor L SerebruanyDominick J Angiolillo
Mar 5, 2010·Journal of Cardiovascular Pharmacology and Therapeutics·Jeanne LoughlinJohn D Seeger
Sep 9, 2011·Naunyn-Schmiedeberg's Archives of Pharmacology·Deborah L HigginsDavid T Beattie

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Citations

Jan 27, 2021·Journal of the American Heart Association·Mervyn B Forman Brewer
May 29, 2021·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Brian E LacyWilliam D Chey

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Methods Mentioned

BETA
flow cytometry
blood collection
urine collection
enzyme-linked immunoassay

Software Mentioned

Aggrolink
SAS

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