Time course inhibition of gastric and platelet COX activity by acetylsalicylic acid in humans

Mark Feldman, Kenneth Shewmake, Byron Cryer

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Aspirin causes peptic ulcers predominately by reducing gastric mucosal cyclooxygenase (COX) activity and prostaglandin synthesis. Because aspirin circulates for only a few hours, we hypothesized that aspirin's inhibitory effect on gastric COX activity must be prolonged. We performed a placebo-controlled experiment in healthy humans to determine the duration of inhibition of aspirin on gastric mucosal COX activity (PGE2 and PGF2(α) synthesis rates). Recovery of gastric COX activity after stopping aspirin was slow and linear. Seventy-two hours after 325-mg aspirin, gastric COX activity was still reduced by 57% (P < 0.001). Duration of inhibition of gastric COX activity was estimated to be 7-8 days after 325-mg aspirin and 5 days after 81-mg aspirin. Recovery of gastric prostaglandin synthesis after 325-mg but not after 81-mg aspirin occurred at slower rates in subjects with Helicobacter pylori-associated gastritis than in those with normal histology. In conclusion, aspirin inhibits gastric COX activity for much longer than predicted from its pharmacokinetic profile, explaining why aspirin at widely spaced intervals is ulcerogenic.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume279
Issue number5 42-5
StatePublished - 2000

Fingerprint

Prostaglandin-Endoperoxide Synthases
Aspirin
Stomach
Blood Platelets
Dinoprost
Gastritis
Peptic Ulcer
Dinoprostone
Helicobacter pylori
Prostaglandins
Histology
Pharmacokinetics
Placebos

Keywords

  • Helicobacter pylori
  • Prostaglandins
  • Thromboxanes
  • Ulcer

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Time course inhibition of gastric and platelet COX activity by acetylsalicylic acid in humans. / Feldman, Mark; Shewmake, Kenneth; Cryer, Byron.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 279, No. 5 42-5, 2000.

Research output: Contribution to journalArticle

@article{73bbdb9fae844d85a99a6f92d3653441,
title = "Time course inhibition of gastric and platelet COX activity by acetylsalicylic acid in humans",
abstract = "Aspirin causes peptic ulcers predominately by reducing gastric mucosal cyclooxygenase (COX) activity and prostaglandin synthesis. Because aspirin circulates for only a few hours, we hypothesized that aspirin's inhibitory effect on gastric COX activity must be prolonged. We performed a placebo-controlled experiment in healthy humans to determine the duration of inhibition of aspirin on gastric mucosal COX activity (PGE2 and PGF2(α) synthesis rates). Recovery of gastric COX activity after stopping aspirin was slow and linear. Seventy-two hours after 325-mg aspirin, gastric COX activity was still reduced by 57{\%} (P < 0.001). Duration of inhibition of gastric COX activity was estimated to be 7-8 days after 325-mg aspirin and 5 days after 81-mg aspirin. Recovery of gastric prostaglandin synthesis after 325-mg but not after 81-mg aspirin occurred at slower rates in subjects with Helicobacter pylori-associated gastritis than in those with normal histology. In conclusion, aspirin inhibits gastric COX activity for much longer than predicted from its pharmacokinetic profile, explaining why aspirin at widely spaced intervals is ulcerogenic.",
keywords = "Helicobacter pylori, Prostaglandins, Thromboxanes, Ulcer",
author = "Mark Feldman and Kenneth Shewmake and Byron Cryer",
year = "2000",
language = "English (US)",
volume = "279",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "5 42-5",

}

TY - JOUR

T1 - Time course inhibition of gastric and platelet COX activity by acetylsalicylic acid in humans

AU - Feldman, Mark

AU - Shewmake, Kenneth

AU - Cryer, Byron

PY - 2000

Y1 - 2000

N2 - Aspirin causes peptic ulcers predominately by reducing gastric mucosal cyclooxygenase (COX) activity and prostaglandin synthesis. Because aspirin circulates for only a few hours, we hypothesized that aspirin's inhibitory effect on gastric COX activity must be prolonged. We performed a placebo-controlled experiment in healthy humans to determine the duration of inhibition of aspirin on gastric mucosal COX activity (PGE2 and PGF2(α) synthesis rates). Recovery of gastric COX activity after stopping aspirin was slow and linear. Seventy-two hours after 325-mg aspirin, gastric COX activity was still reduced by 57% (P < 0.001). Duration of inhibition of gastric COX activity was estimated to be 7-8 days after 325-mg aspirin and 5 days after 81-mg aspirin. Recovery of gastric prostaglandin synthesis after 325-mg but not after 81-mg aspirin occurred at slower rates in subjects with Helicobacter pylori-associated gastritis than in those with normal histology. In conclusion, aspirin inhibits gastric COX activity for much longer than predicted from its pharmacokinetic profile, explaining why aspirin at widely spaced intervals is ulcerogenic.

AB - Aspirin causes peptic ulcers predominately by reducing gastric mucosal cyclooxygenase (COX) activity and prostaglandin synthesis. Because aspirin circulates for only a few hours, we hypothesized that aspirin's inhibitory effect on gastric COX activity must be prolonged. We performed a placebo-controlled experiment in healthy humans to determine the duration of inhibition of aspirin on gastric mucosal COX activity (PGE2 and PGF2(α) synthesis rates). Recovery of gastric COX activity after stopping aspirin was slow and linear. Seventy-two hours after 325-mg aspirin, gastric COX activity was still reduced by 57% (P < 0.001). Duration of inhibition of gastric COX activity was estimated to be 7-8 days after 325-mg aspirin and 5 days after 81-mg aspirin. Recovery of gastric prostaglandin synthesis after 325-mg but not after 81-mg aspirin occurred at slower rates in subjects with Helicobacter pylori-associated gastritis than in those with normal histology. In conclusion, aspirin inhibits gastric COX activity for much longer than predicted from its pharmacokinetic profile, explaining why aspirin at widely spaced intervals is ulcerogenic.

KW - Helicobacter pylori

KW - Prostaglandins

KW - Thromboxanes

KW - Ulcer

UR - http://www.scopus.com/inward/record.url?scp=0033668232&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033668232&partnerID=8YFLogxK

M3 - Article

C2 - 11053009

AN - SCOPUS:0033668232

VL - 279

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 5 42-5

ER -