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 p rostaglandins appears to be central to the mechanisms involved in aspi rin sensitivity. We have investigated whether the plasma levels of ace tylsalicylic 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 asp irin. ASA and SA concentrations in plasma were determined by HPLC. Aft er oral provocation (up to 460 mg cumulative dose), the levels of ASA and SA in plasma were equivalent in aspirin-sensitive and aspirin-tole rant subjects. For the aspirin-sensitive subjects, at the time of adve rse reaction, the concentration range was 2.9-33.3 mu M for ASA and 18 .1-245 mu M for SA. Oral provocation with sodium salicylate yielding 1 0-fold higher SA levels did not elicit intolerance reactions. Statisti cally significantly lower levels of ASA and SA (P less than or equal t o 0.01) evoked airway obstruction, as compared with merely extrapulmon ary symptoms. Bronchial absorption of aspirin was found after inhalati on of lysine-aspirin and was comparable in asthmatic and nonasthmatic subjects. In three aspirin-sensitive subjects who developed airway obs truction, the plasma levels for ASA and SA were 0.9-2.6 mu M and 0.0-6 .7 mu M, respectively. In conclusion, the plasma levels of ASA reached at the time of a positive reaction are of the magnitude known to inhi bit cyclo-oxygenases. Neither differences in bioavailability of ASA no r the formation of SA seems to contribute to the aspirin-elicited reac tions.