Aspirin-sensitive asthma: significance of the cyclooxygenase-inhibiting and protein-binding properties of analgesic drugs.
The in vitro release of endogenous and exogenous PgF2 alpha from plasma and serum proteins by aspirin and other analgesic drugs has been studied by RIA and equilibrium-dialysis techniques, respectively. Before aspirin addition, the mean plasma level of PgF2 alpha measured by RIA was significantly lower in aspirin-sensitive asthma (ASA) patients (11.3 +/- 6.5 pg/ml; n = 8) than in aspirin-tolerant asthma (ATA) patients (25.0 +/- 11.4 pg/ml; n = 21). After aspirin addition (50 micrograms/ml) the mean PgF2 alpha level detected in plasma by RIA was higher in ASA patients (97.6 +/- 5.5 pg/ml) than in ATA patients (66.9 +/- 4.5). The binding of [3H]PgF2 alpha to serum protein was significantly inhibited by NSAIDs but not by paracetamol (0.2-1.0 mM). These results implicate PgF2 alpha and the protein-binding property of analgesic drugs in the pathogenesis of aspirin-sensitive asthma.
Williams
W R
WR
Asthma and Allergy Unit, Sully Hospital, Cardiff, UK.
Pawlowicz
A
A
Davies
B H
BH
D000082:Acetaminophen / Q000494:pharmacology; D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy*; D015237:Dinoprost / Q000378:metabolism; D004361:Drug Tolerance / Q000502:physiology*; D005260:Female; D005439:Flufenamic Acid / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008528:Mefenamic Acid / Q000494:pharmacology; D008875:Middle Aged; D010653:Phenylbutazone / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects
D000082:Acetaminophen; D008528:Mefenamic Acid; D005439:Flufenamic Acid; D015237:Dinoprost; D011451:Prostaglandin-Endoperoxide Synthases; D010653:Phenylbutazone; D001241:Aspirin; D007213:Indomethacin