salicylates and gentisuric-acid

The transport of aspirin (ASP) and its metabolites (salicylic acid (SA), salicyluric acid (SAU), gentisic acid (GA) and gentisuric acid (GAU)) through human erythrocyte membrane was investigated. ASP permeated rapidly into the erythrocytes and the concentration dwindled gradually after the maximum concentration was attained almost within one minute. It was suggested that SA is released from the erythrocytes after ASP transported into the erythrocytes is hydrolyzed in them. In both an inward and outward direction, the transport rates of SA and GA were rapid, while those of SAU and GAU were lower by conjugating glycine. It was suggested that GAU remains for a long time in a living body. The rate of transport of GA and GAU were markedly obstructed by the band 3 protein inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonate, although the transport rates of SA and SAU were obstructed only slightly. It was suggested that the transport of GA and GAU are mediated through band 3 protein.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Aspirin; Chemical Phenomena; Chemistry, Physical; Culture Media; Cytosol; Erythrocyte Membrane; Gentisates; Hippurates; Humans; Hydrolysis; Hydroxybenzoates; In Vitro Techniques; Salicylates; Salicylic Acid

1. Metabolism of aspirin was studied in 10 human volunteers who took a therapeutic dose (600 mg) by mouth and in nine patients who took aspirin in overdose. 2. Salicyluric acid was the major urinary metabolite in volunteers (63.1 +/- 8.4% of dose in 0-8 h). In overdose patients, salicyluric acid in urine was decreased (30.0 +/- 8.2%, 0-24 h, P less than 0.001) and there was increased elimination of salicyclic acid (34.1%, P less than 0.005), salicyl acyl glucuronide (14.4%, P less than 0.05) and gentisuric acid (5.3%). 3. Metabolism of orally administered 14C-aspirin in rats over a 10-fold dose range (10-100 mg/kg) resulted in excretion of 81-91% dose in urine in the first 24 h. Salicyclic acid was the major urinary metabolite (43-51% dose). Excretion of salicyluric acid decreased with increasing dose, whereas gentisic acid and salicyl phenolic and acyl glucuronides increased. 4. The profile of aspirin metabolites was qualitatively similar in man and rat but there were quantitative differences. Limited capacity to form salicyluric acid was observed in both species. Dependence on this pathway in rat was low and was compensated by increased utilization of other routes; dependence on salicyluric acid formation in man was high and in overdose, compensation by other routes was incomplete.

Topics: Adolescent; Adult; Animals; Aspirin; Female; Gentisates; Glucuronates; Hippurates; Humans; Kinetics; Male; Middle Aged; Rats; Rats, Inbred Strains; Salicylates; Salicylic Acid