ACTION OF METHOTREXATE ON CYTOCHROME-P-450 MONOOXYGENASES IN RATS - STUDY PERFORMED WITH [C-13]-AMINOPYRINE MICRO BREATH TEST

The aim of this work was to study the action of methotrexate on the cy tochrome P-450 hepatic monooxygenases and to follow the evolution of t he metabolic processes with time, after oral and intra-peritoneal admi nistration of these drugs to rats. In order to perform this study, we used a new technique the [C-13]-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 amin opyrine N-demethylase, 7-ethoxyresorufin desalkylase, 7-ethoxycoumarin desalkylase, 7-pentoxyresorufin desalkylase were determined. A histol ogical study of the liver was also carried out. Finally, haematologica l and biochemical parameters were also determined. In this study, 3 se ries 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 observatio n, 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.