Renal accumulation of salicylate and phenacetin: possible mechanisms in the nephropathy of analgesic abuse.
Since either aspirin or phenacetin might be causative in the nephropathy of analgesic abuse, studies were designed to examine the renal accumulation and distribution of the major metabolic products of these compounds, salicylate and N-acetyl-p-aminophenol (APAP) respectively, in dogs. Nineteen hydropenic animals were studied, of which seven were given phenacetin, nine received acetyl salicylic acid, two were given both aspirin and phenacetin, and one received APAP directly. Two of three hydrated animals were given phenacetin and one was given aspirin. During peak blood levels of salicylate and (or) APAP, the kidneys were rapidly removed, frozen, sliced from cortex to papillary tip, and analyzed for water, urea, APAP, and salicylate. No renal medullary gradient for salicylate was demonstrable during both hydropenic and hydrated states. In contrast, both free and conjugated APAP concentrations rose sharply in the inner medulla during hydropenia, reaching a mean maximal value at the papillary tip exceeding 10 times the cortical concentration (P < 0.001), a distribution similar to that of urea. Salicylate had no effect on the APAP gradient, but hydration markedly reduced both the APAP and urea gradients in the medulla. The data indicate that APAP probably shares the same renal mechanisms of transport and accumulation as urea and acetamide, and that papillary necrosis from excessive phenacetin may be related to high papillary concentration of APAP.
D000700:Analgesics; D000818:Animals; D001241:Aspirin / Q000032:analysis / Q000494:pharmacology; D003681:Dehydration / Q000503:physiopathology; D004285:Dogs; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000032:analysis*; D007671:Kidney Concentrating Ability; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology; D007681:Kidney Papillary Necrosis / Q000503:physiopathology; D009995:Osmosis; D010615:Phenacetin / Q000032:analysis* / Q000097:blood / Q000494:pharmacology / Q000652:urine; D012459:Salicylates / Q000032:analysis* / Q000097:blood / Q000652:urine; D019966:Substance-Related Disorders; D014508:Urea / Q000032:analysis
D000700:Analgesics; D012459:Salicylates; D014508:Urea; D010615:Phenacetin; D001241:Aspirin