代谢
研究了雄性大鼠对2-氨基-3-甲基咪唑[4,5-f]喹啉（IQ）的代谢，使用分子中第2和第5位的^14C和^3H同位素。成年雄性Fischer 344大鼠通过口服灌胃给予[2-^14C]IQ或[5-^3H]IQ，剂量为20或40毫克/千克体重。在大鼠的饮食中给予[2-^14C]IQ，剂量为300 ppm，持续2天，并在大约6.5周的未标记IQ（300 ppm）饮食后，再给予2天。在口服20或40毫克[2-^14C]IQ/千克体重后的最初48小时内，大约40-50%的放射性物质在尿液中回收，大约30-38%的放射性物质在粪便中回收。在饮食中摄入[2-^14C]IQ（300 ppm）后的最初72小时内，大约26%的放射性物质在尿液中回收，大约61%的放射性物质在粪便中回收。在大鼠口服灌胃单次剂量[2-^14C]IQ（40毫克/千克体重）并引流胆管后，2天内胆汁中排泄了约15%的给药剂量。给予[2-^14C]IQ的大鼠尿液中含有三种主要极性代谢物，包括一种葡萄糖苷酸、一种硫酸酯和IQ磺酰胺，以及一些较少极性的代谢物，包括IQ、2-乙酰氨基-3-甲基咪唑[4,5-f]喹啉、2-氨基咪唑[4,5-f]喹啉和2-氨基-3,6-二氢-3-甲基-7H-咪唑[4,5-f]喹啉-7-酮（7-OH-IQ）。口服灌胃或饮食给予[2-^14C]IQ产生了相同的代谢物，但数量不同。在口服灌胃给予[2-^14C]的大鼠粪便中，IQ磺酰胺是极性组分中的主要代谢物。尿液中发现的类似非极性代谢物也存在于粪便中，但数量不同。一个主要的非极性粪便代谢物，7-OH-IQ可能是由于肠道细菌菌群的活动产生的。在一次口服灌胃给予[2-^14C]IQ的大鼠中，尿液中代谢物的排泄高于饮食给予[2-^14C]IQ的动物，而粪便中的排泄则较低。尿液中的一种极性代谢物，IQ磺酰胺（39%）在口服给予IQ的大鼠中的水平显著高于饮食给予IQ的大鼠（小于6%）。因此，IQ被广泛代谢，产生许多极性和非极性代谢物，其数量部分取决于给药方式。
The metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was studied in the male rat using ... 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 ... 20 or 40 mg/kg bw. Rats were also given [2-14C]IQ in the diet at ... 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 feces. In the initial 72 hr following consumption of [2-14C]IQ (300 ppm) in the diet about 26% /of the/ radioactivity was recovered in the urine and about 61% /of the/ radioactivity was recovered in the feces. Following cannulation of the bile ducts, rats administered a single dose of [2-14C]IQ (40 mg/kg bw) 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 sulfate ester and IQ sulfamate, 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 feces of rats given [2-14C] by oral gavage, IQ-sulfamate 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 fecal 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 feces compared with that in animals fed [2-14C]IQ in the diet. One polar metabolite present in the urine, IQ-sulfamate (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.
来源:Hazardous Substances Data Bank (HSDB)
