Effect of other drugs and chemicals on the degradation of aspirin in vitro: possible extrapolation to in vivo metabolism of aspirin

Abstract

To assess the possible influence of other drugs and chemicals on the metabolic degradation of aspirin in man, their effect on the serum aspirin esterase activity was determined in vitro. The activation or inhibition of the enzyme as observed with these compounds suggest the possibility that simultaneous ingestion of these drugs with aspirin may influence the pharmacology and toxicity of the analgesic.

PIP: The action of various drugs and chemicals on the serum aspirin esterase activity was tested as a measure of their possible effect on the metabolic degradation of aspirin in order to elucidate how the interaction between drugs and aspirin may influence aspirin's pharmacology and toxicity. The in vitro test used serum as the source of the enzyme which was incubated with soluble aspirin as substrate followed by treatment with an acidic reagent of mercuric chloride and ferric nitrate, which precipitates the serum proteins. The following drugs were found to act as inhibitors of serum aspirin esterase activity: codeine phosphate (50%), dextropropoxyphene (Doloxen and Digestic both 50%), morphine, methadone, pethidine, papaveretum (all 50%), hydroxychloroquine (Plaquenil 50%), heparin (50%), propanolol (Inderal 50%), cimetidien (Tagamet 50%), alcohol (50%), and ascorbic acid (50%). The following drugs were activators of aspirin esterase: calcium (50%) and magnesium (50%). The following drugs were found inactive: paracetamol, caffeine, phenacetin, phyenylbutazone (Butazolidine), indomethacin (Indocid), cortisone acetate, flufenamic acid (Arlef), mefenamic acid (Ponstan), Ibuprofen (Brufen), dipyridamole (Persantin), warfarin (Coumadin), clofibrate (Atromid), sulphinpyrazone (Anturan), colchincine, allopurinol, diazepam (Valium), oral contraceptives, and sodium cromoglycate (Intal).