Action of methotrexate on cytochrome P-450 monooxygenases in rats. Study performed with [13C]-aminopyrine micro breath test.
The aim of this work was to study the action of methotrexate on the cytochrome P-450 hepatic monooxygenases and to follow the evolution of the metabolic processes with time, after oral and intra-peritoneal administration of these drugs to rats. In order to perform this study, we used a new technique the [13C]-aminopyrine breath test (ABT). At the end of the in vivo study, the rats were sacrificed and the cytochrome P-450 concentration as well as microsomal enzymatic activities of aminopyrine N-demethylase, 7-ethoxyresorufin desalkylase, 7-ethoxycoumarin desalkylase, 7-pentoxyresorufin desalkylase were determined. A histological study of the liver was also carried out. Finally, haematological and biochemical parameters were also determined. In this study, 3 series of 6 rats were used: a control group, a group receiving 70 mg/kg of methotrexate by intra-peritoneal route, and a group of rats treated orally with 1 mg/kg of methotrexate every 2 days. For each observation, the variation of the ABT scores and of the cytochrome P-450 amounts as well as the microsomal aminopyrine N-demethylase activity were in good agreement.
Guitton
J
J
Laboratoire d'Etudes Analytiques et Cinétiques du Médicament, Institut des Sciences Pharmaceutiques et Biologiques de Lyon, France.
Souillet
G
G
Rivière
J L
JL
Gerard
F
F
Guilluy
R
R
Brazier
J L
JL
D000284:Administration, Oral; D000632:Aminopyrine; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001944:Breath Tests; D002247:Carbon Isotopes; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010105:Oxygenases / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D002247:Carbon Isotopes; D000632:Aminopyrine; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000633:Aminopyrine N-Demethylase; D008727:Methotrexate