Depression of the hepatic cytochrome P 450 mono oxygenase system by administered tilorone (2,7 bis[2 (diethylamino)ethoxy]fluoren 9 one dihydrochloride)

The oral administration of the antiviral agent, tilorone . HCl (50 mg/day for 4 days) to rats caused losses of hepatic microsomal ethylmorphine N demethylase, benzo[a]pyrene hydroxylase and aniline hydroxylase activities of 50, 44 and 22%, respectively. Microsomal levels of cytochrome P 450 and NADPH cytochrome c reductase were lowered by 40 and 20% respectively, but levels of cytochrome b₅ and NADH cytochrome c reductase remained unchanged. After a single oral dose of tilorone . HCl(50 mg/kg) a loss of 38% of the microsomal cytochrome P450 and 25% of the ethylmorphine N demethylase activity was observed within 24 hr; recovery was complete within 8 to 10 days. Hexobarbital sleeping times and blood levels were elevated after tilorone administration (20 or 50 mg/kg/day for 4 days). In vitro, tilorone HCl showed no inhibitory effect on microsomal drug metabolism nor did it affect the cytochrome P 450 content of the microsomes. The rate of incorporation of δ amino[³H] levulinic acid into cytochrome P 450 was not affected by tilorone HCl.