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Dose-dependent change in the pattern of phenacetin metabolism in man and its possible significance in analgesic nephropathy

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Summary

Ten healthy volunteers were given twice a single dose of phenacetin, 0,5 g in the first and 2,5 g in the second experiment carried out one week later. Based on the pattern of phenacetin metabolism elaborated by Büchet al. [5] phenacetin, total acetyl-p-aminophenol, p-phenetidine and 2-hydroxyphenetidinesulfate were estimated in the urine which was collected for 12 hours after ingestion of the drug.

The results obtained reveal a shift in the metabolic degradation of phenacetin from simply raising the dose. While the average output of total acetyl-p-aminophenol and of phenacetin (expressed in percentage of the dose) is similar with both doses, the formation and output of p-phenetidine and of 2-hydroxyphenetidinesulfate are enhanced with the higher dose.

As a working hypothesis for further investigation it is assumed, that in the attempt to elucidate the pathogenesis of analgesic nephropathy the metabolite phenetidine deserves special consideration.

Zusammenfassung

Ergebnisse von Versuchen über den Metabolismus von Phenacetin bei 10 Normalpersonen zeigen, daß die Metabolisierung dosisabhängige Charakteristica aufweist, indem bei einer Erhöhung der Einzeldosis von 0,5 auf 2,5 g die im 12 Std-Harn ausgeschiedenen Mengen von Phenetidin und 2-Hydroxyphenetidinsulfat (ausgedrückt in Dosisprozenten) um angenähert das Vierfache zunehmen. Demgegenüber bleiben die ausgeschiedenen Dosisprozente des totalen N-Acetylaminophenols (frei und konjugiert) und von Phenacetin unverändert.

Als Arbeitshypothese für weitere Versuche wird angenommen, daß in der Pathogenese der chronisch interstitiellen Nephritis im Anschluß an Abusus von phenacetinhaltigen Analgetica dem Phenacetinmetaboliten Phenetidin eine besondere Bedeutung zukommt.

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Authors and Affiliations

  1. Department of Experimental Medicine, F. Hoffmann-LaRoche & Co., Ltd., Basle, Switzerland

    J. Raaflaub & U. C. Dubach

  2. Medical Policlinic of the University, Basle, Switzerland

    J. Raaflaub & U. C. Dubach

Authors
  1. J. Raaflaub
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  2. U. C. Dubach
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Raaflaub, J., Dubach, U.C. Dose-dependent change in the pattern of phenacetin metabolism in man and its possible significance in analgesic nephropathy. Klin Wochenschr 47, 1286–1287 (1969). https://doi.org/10.1007/BF01487561

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