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Elimination of phenacetin and phenazone by man before and after treatment with phenobarbital

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Summary

After the oral administration to volunteers of phenacetin (15 mg/kg) the highest concentration in blood was reached 2 h later. The decline appeared to follow first order kinetics with an apparent biological half-life (t′/2) of 0.8 h. The highest concentration in blood of the unconjugated metabolite, paracetamol, was twice that of phenacetin. About 70 per cent of a dose of phenacetin was excreted as conjugated paracetamol in the urine, and 70 per cent of this compound was eliminated during the first 12 h period. — After daily administration of 1.4, 2.5 and 3.6 mg/kg of Phenobarbital, each dose sequentially for 1 week, the apparent biological half-life of phenacetin and the elimination rates of its metabolites, unconjugated and conjugated paracetamol, remained unchanged. The elimination rate of phenazone (16 mg/kg) was increased by 40 per cent in the same subjects after treatment with phenobarbital. — The blood concentration of phenacetin varied more than 20 times between individuals, although no individual variation was found for the blood levels of unconjugated paracetamol.

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Parts of this paper have been published in a short communication [11] and at the 11. Frühjahrstagung der Deutschen Pharmakologischen Gesellschaft on March 15–18, 1970 [12].

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Kampffmeyer, H.G. Elimination of phenacetin and phenazone by man before and after treatment with phenobarbital. Eur J Clin Pharmacol 3, 113–118 (1971). https://doi.org/10.1007/BF00619304

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Key-words

  • Enzyme-induction
  • man
  • phenacetin
  • phenazone