title: Antipyrine and caffeine dispositions in clinically normal dogs and dogs with progressive liver disease.
abstract: Dispositions of caffeine and antipyrine were compared as indicators of decreasing hepatic function in dogs with experimentally induced progressive 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: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of antipyrine, and 24 hours later, caffeine was studied 3 weeks after the last dose of toxin in each dog. For both drugs, rapid 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 < or = 0.01). Clearance of antipyrine and caffeine was decreased in groups 3 and 4, compared with groups 1 and 2. Antipyrine and caffeine mean residence times were longer in group-3 dogs, compared with dogs of groups 1 and 2. Correction of caffeine and antipyrine clearances for hepatic weight increased discrimination between groups 3 and 4. The clearance and mean residence time ratios of antipyrine to caffeine were calculated for each group and, when compared with values for group-1 dogs, were used to test for differences between the 2 drugs in response to disease. Ratios did not differ among groups. These results indicate that the disposition of antipyrine and caffeine may change similarly with progression of dimethylnitrosamine-induced liver disease.
authors.affiliation: Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station 77843-4466.
authors.forename: D M
authors.initials: DM
authors.lastname: Boothe
authors.forename: J M
authors.initials: JM
authors.lastname: Cullen
authors.forename: J A
authors.initials: JA
authors.lastname: Calvin
authors.forename: W L
authors.initials: WL
authors.lastname: Jenkins
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
authors.forename: R A
authors.initials: RA
authors.lastname: Green
authors.forename: D E
authors.initials: DE
authors.lastname: Corrier
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000983:Antipyrine / Q000097:blood / Q000493:pharmacokinetics*; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics*; D056486:Chemical and Drug Induced Liver Injury; D002851:Chromatography, High Pressure Liquid; D004128:Dimethylnitrosamine / Q000633:toxicity*; D004285:Dogs; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D012016:Reference Values
chemical_list: D002110:Caffeine; D004128:Dimethylnitrosamine; D000983:Antipyrine