NON-INDUCTION OF EXTRAHEPATIC ANTIPYRINE AND METRONIDAZOLE METABOLISMEVALUATED FROM PARTIALLY HEPATECTOMIZED RATS

1. The effect of beta-naphthofiavone (BNF), given i.p. (n = 9) and ora lly (n = 9), on the metabolism of antipyrine and metronidazole was inv estigated in rats. 2. The clearances of antipyrine and metronidazole w ere determined on a single saliva sample. The rates of formation of an tipyrine and metronidazole metabolites were determined from a 20 h uri ne sample and saliva clearance. 3. Administration of beta-naphthoflavo ne i.p. was significantly more effective than oral dosage on the induc tion of antipyrine and metronidazole metabolism (p < 0.05). 4. The cap acity of extrahepatic tissues to metabolize antipyrine and metronidazo le was quantitatively assessed in rats with and without pretreatment w ith beta-naphthoflavone immediately after sham operation or 70% partia l hepatectomy (n = 40). 5. Antipyrine and metronidazole clearances cor related with liver weight in induced and non-induced rats. Linear regr ession of antipyrine and metronidazole clearances did show a non-signi ficant Y-intercept (p > 0.05), indicating a negligible extrahepatic me tabolism in both induced and in non-induced rats. 6. From a quantitati ve point of view this study indicates that induction of extrahepatic c ytochrome P450 metabolism of antipyrine and metronidazole is negligibl e.