Influence of acute and chronic administration of methadone hydrochloride on NADPH cytochrome c reductase and cytochrome P 450 of mouse liver microsomes

Administration of a single acute dose (20 mg/kg body weight) of methadone hydrochloride to both male and female mice increased the specific activity of NADPH cytochrome c reductase and did not change much the content of cytochrome P 450 of their liver microsomes. Administration of multiple acute doses of methadone in male mice increased the specific activity of cytochrome c reductase and the content of cytochrome P 450 of their liver microsomes. Chronic administration of progressively increasing doses of methadone (up to 40 mg/kg body weight) to male mice increased the specific activity of c reductase. Similar chronic administration of methadone up to 28 mg/kg body weight also increased the microsomal content of P 450, but with higher doses of methadone, the content of P 450 declined and finally dropped slightly below control levels. The levels of c reductase activity and P 450 content returned to normal about two weeks after discontinuation of methadone administration.