Metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline in the male rat.

The metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was studied in the male rat using the radiochemical labels 14C and 3H at positions 2 and 5 of the molecule, respectively. Adult male Fischer 344 rats were administered [2-14C]IQ or [5-3H]IQ by oral gavage at dose levels of 20 or 40 mg/kg body weight. Rats were also given [2-14C]IQ in the diet at a dose level of 300 ppm for 2 days and after administration of unlabelled IQ (300 ppm) in the diet for approximately 6.5 wk for an additional 2 days. In the initial 48 hr following oral administration of 20 or 40 mg [2-14C]IQ/kg body weight, about 40-50% radioactivity was recovered in the urine, and about 30-38% radioactivity was recovered in the faeces. In the initial 72 hr following consumption of [2-14C]IQ (300 ppm) in the diet about 26% radioactivity was recovered in the urine and about 61% radioactivity was recovered in the faeces. Following cannulation of the bile ducts, rats administered a single dose of [2-14C]IQ (40 mg/kg body weight) by oral gavage excreted about 15% of the administered dose in the bile over a period of 2 days. Urine from rats given [2-14C]IQ contained three main polar metabolites that included a glucuronide, a sulphate ester and IQ sulphamate, and a number of less polar metabolites that included IQ, 2-acetylamino-3-methylimidazo[4,5-f]quinoline, 2-aminoimidazo[4,5-f]quinoline and 2-amino-3,6-dihydro-3-methyl-7H-imidazo[4,5-f]quinoline-7-one (7-OH-IQ). Administration of [2-14C]IQ by oral gavage or in the diet gave the same metabolites, but in different amounts. In the faeces of rats given [2-14C] by oral gavage, IQ-sulphamate was the major metabolite in the polar fraction. Non-polar metabolites similar to those found in the urine were also present, but in different amounts. A major, non-polar faecal metabolite, 7-OH-IQ was probably formed as a result of the activity of the intestinal bacterial flora. In rats given a single gavage dose of [2-14C]IQ, excretion of metabolites was higher in the urine and lower in the faeces compared with that in animals fed [2-14C]IQ in the diet. One polar metabolite present in the urine, IQ-sulphamate (39%), was found at considerably higher levels in rats dosed orally with IQ compared with those fed IQ (less than 6%). Thus, IQ is extensively metabolized to give a number of polar and non-polar metabolites, the amounts of which depend, in part, on the mode of dosing.