ANTIPYRINE AND CAFFEINE DISPOSITIONS IN CLINICALLY NORMAL DOGS AND DOGS WITH PROGRESSIVE LIVER-DISEASE

Dispositions of caffeine and antipyrine were compared as indicators of decreasing hepatic function in dogs with experimentally induced progr essive liver disease, Dimethylnitrosamine, a hepatospecific toxin, was administered orally to 16 dogs; 6 dogs served as controls (group 1). Three classes of liver disease were defined by histologic features: mi ld (group 2; n= 5), moderate (group 3; n= G), and severe (group 4; n= 5). Disposition of antipyrine, and 24 hours later, caffeine was studie d 3 weeks after the last dose of toxin in each dog. For both drugs, ra pid IV administration of 20 mg/kg of body weight was administered and serum samples were obtained at intervals for determination of at least 5 terminal-phase drug half-lives. For both drugs, clearance and mean residence time differed among groups (P less than or equal to 0.01). C learance of antipyrine and caffeine was decreased in groups 3 and 4, c ompared with groups 1 and 2. Antipyrine and caffeine mean residence ti mes were longer in group-3 dogs, compared with dogs of groups 1 and 2. Correction of caffeine and antipyrine clearances for hepatic weight i ncreased discrimination between groups 3 and 4, The clearance and mean residence time ratios of antipyrine to caffeine were calculated for e ach group and, when compared with values for group-1 dogs, were used t o test for differences between the 2 drugs in response to disease. Rat ios did not differ among groups. These results indicate that the dispo sition of antipyrine and caffeine may change similarly with progressio n of dimethylnitrosamine-induced liver disease.