TY - JOUR T1 - Depression of the hepatic cytochrome P-450 mono-oxygenase system by administered tilorone (2,7-bis(2-(diethylamino)ethoxy)fluoren-9-one dihydrochloride). JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 223 LP - 231 VL - 4 IS - 3 AU - K W Renton AU - G J Mannering Y1 - 1976/05/01 UR - http://dmd.aspetjournals.org/content/4/3/223.abstract N2 - 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 P-450 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 nod did it affect the cytochrome P-450 content of the microsomes. The rate of incorporation of delta-amino(3H)levulinic acid into cytochrome P-450 was not affected by tilorone-HCl. ER -