INFLUENCE OF LIVER-DAMAGE ON ANTIPYRINE METABOLITE FORMATION IN RATS

1. The effects of three types of liver damage induced by carbon tetrachloride (CCl4), D-galactosamine (Ga1N) and alpha-naphthylisothiocyanate (ANIT) on antipyrine (AP) metabolism was studied in rats. 2. The serum half-life (t1/2) of AP (50 mg/kg, i.p.) was increased and total body clearance (CL) decreased in all three types of liver damage; the apparent volume of distribution (V(d)) was relatively unchanged. 3. Rates of formation of AP metabolites (CL(m)) were lower than those in the control group in all three types of liver damage. 4. Rates of urinary excretion (% dose) of AP metabolites, 3-hydroxymethylantipyrine (HMA) and 3-hydroxymethyl-3-norantipyrine (NORA) were decreased in all three types of liver damage. However, the rate for 4-hydroxyantipyrine (OHA) was lower only in the Ga1N-treated rats. 5. The percentage conjugation of HMA was higher in the ANIT-treated rats than in the control group, and percentage conjugation of NOR was lower only in the Ga1N-treated rats. 6. These results indicate that the pathways of oxidation and conjugation of AP metabolism are not affected to the same extents by different types of liver damage.