Plasma acetylsalicylic acid and salicylic acid levels during aspirin provocation in aspirin-sensitive subjects.
The ability of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit the cyclo-oxygenase which catalyzes formation of prostaglandins appears to be central to the mechanisms involved in aspirin sensitivity. We have investigated whether the plasma levels of acetylsalicylic acid (ASA) and its main metabolite salicylic acid (SA) at the time of intolerance reactions correspond with the concentrations required for enzyme inhibition in vitro. Twelve aspirin-sensitive and 15 aspirin-tolerant subjects were followed during provocation with aspirin. ASA and SA concentrations in plasma were determined by HPLC. After oral provocation (up to 460 mg cumulative dose), the levels of ASA and SA in plasma were equivalent in aspirin-sensitive and aspirin-tolerant subjects. For the aspirin-sensitive subjects, at the time of adverse reaction, the concentration range was 2.9-33.3 microM for ASA and 18.1-245 microM for SA. Oral provocation with sodium salicylate yielding 10-fold higher SA levels did not elicit intolerance reactions. Statistically significantly lower levels of ASA and SA (P < or = 0.01) evoked airway obstruction, as compared with merely extrapulmonary symptoms. Bronchial absorption of aspirin was found after inhalation of lysine-aspirin and was comparable in asthmatic and nonasthmatic subjects. In three aspirin-sensitive subjects who developed airway obstruction, the plasma levels for ASA and SA were 0.9-2.6 microM and 0.0-6.7 microM, respectively. In conclusion, the plasma levels of ASA reached at the time of a positive reaction are of the magnitude known to inhibit cyclo-oxygenases. Neither differences in bioavailability of ASA nor the formation of SA seems to contribute to the aspirin-elicited reactions.
Dahlén
B
B
Department of Thoracic Medicine, Karolinska Hospital, Stockholm, Sweden.
Boréus
L O
LO
Anderson
P
P
Andersson
R
R
Zetterström
O
O
D000284:Administration, Oral; D000328:Adult; D000402:Airway Obstruction / Q000097:blood / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D001241:Aspirin / Q000009:adverse effects* / Q000097:blood* / Q000276:immunology; D001249:Asthma / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D005260:Female; D005541:Forced Expiratory Volume; D016166:Free Radical Scavengers; D006801:Humans; D008297:Male; D008875:Middle Aged; D012459:Salicylates / Q000097:blood*; D020156:Salicylic Acid; D012980:Sodium Salicylate / Q000008:administration & dosage / Q000276:immunology
D016166:Free Radical Scavengers; D012459:Salicylates; D020156:Salicylic Acid; D001241:Aspirin; D012980:Sodium Salicylate