Non-induction of extrahepatic antipyrine and metronidazole metabolism evaluated from partially hepatectomized rats.
1. The effect of beta-naphthoflavone (BNF), given i.p. (n = 9) and orally (n = 9), on the metabolism of antipyrine and metronidazole was investigated in rats. 2. The clearances of antipyrine and metronidazole were determined on a single saliva sample. The rates of formation of antipyrine and metronidazole metabolites were determined from a 20 h urine sample and saliva clearance. 3. Administration of beta-naphthoflavone i.p. was significantly more effective than oral dosage on the induction of antipyrine and metronidazole metabolism (p < 0.05). 4. The capacity of extrahepatic tissues to metabolize antipyrine and metronidazole was quantitatively assessed in rats with and without pretreatment with beta-naphthoflavone immediately after sham operation or 70% partial hepatectomy (n = 40). 5. Antipyrine and metronidazole clearances correlated with liver weight in induced and non-induced rats. Linear regression of antipyrine and metronidazole clearances did show a non-significant Y-intercept (p > 0.05), indicating a negligible extrahepatic metabolism in both induced and in non-induced rats. 6. From a quantitative point of view this study indicates that induction of extrahepatic cytochrome P450 metabolism of antipyrine and metronidazole is negligible.
Jeding
I B
IB
Department of Pharmacology, University of Copenhagen, Denmark.
Loft
S
S
Poulsen
H E
HE
D000284:Administration, Oral; D000818:Animals; D000983:Antipyrine / Q000378:metabolism* / Q000652:urine; D001571:Benzoflavones / Q000008:administration & dosage / Q000494:pharmacology; D006498:Hepatectomy; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D008297:Male; D008795:Metronidazole / Q000378:metabolism* / Q000652:urine; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D012463:Saliva / Q000737:chemistry; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D008795:Metronidazole; D019324:beta-Naphthoflavone; D000983:Antipyrine