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Abstract
1. The metabolism of 3H-acetanilide was studied in rats (a) after a single intraperitoneal dose of 200 mg/kg, (b) after 1–5 days of continuous feeding of 0.8% of labelled acetanilide in the diet, and (c) at weekly intervals during 4 weeks of such feeding. The three experimental groups excreted 56, 62 and 86% of dose, respectively, in 24 h samples of urine.
2. 4-Hydroxyacetanilide, the major metabolite, was found free, as well as conjugated with glucuronic and sulphuric acids in all groups. The glucuronide fraction increased from 4.6% (single i.p. dose), and 6.0% (1 day feeding) to 16% of dose at 1 week. The sulphate conjugate of 4-hydroxyacetanilide decreased from 70% of dose at 24 h to only 43% after 1 week of feeding.
3. Blood levels of radioactivity at 1 week were 11-fold higher than after a single dose. The liver contained 15 times more isotope at 4 weeks than after a single dose. Binding to DNA, RNA and proteins of liver at 4 weeks was 180-, 15- and 33-fold greater, respectively, than the values found after a single i.p. dose.