Enriquez P M, Divincenzo G D
Toxicology. 1984 Feb;29(4):337-43. doi: 10.1016/0300-483x(84)90165-3.
The metabolic fate of [14C]5-amino-1-naphthol (5A1N) was investigated in Sprague-Dawley rats. [14C]5A1N was administered by gastric intubation to male rats at doses 1, 37 and 135 mg/kg body weight. In a separate experiment the rats were also dosed with 150 mg/kg of unlabeled 5A1N daily for 4 consecutive days. Between 74% and 85% of the administered dose was excreted in the urine. Over 98% of the urinary radioactivity was characterized as unchanged 5A1N, 5-acetamido-1-naphthol (5AA1N) and glucuronic and sulfuric acid conjugates of both 5A1N and 5AA1N. Unchanged 5A1N and 5AA1N accounted for less than 3% of the dose. The amount of 5A1N converted to 5AA1N and its conjugates varied inversely with the dose. Two minor metabolites were not identified. Rats dosed repeatedly with 150 mg/kg of 5A1N showed no significant change in metabolite excretion patterns compared to rats dosed singly. These findings indicate that in the rodent model the metabolism of 5A1N was dose dependent, and occurred predominantly by phase II reactions involving N-acetylation and conjugation with glucuronic and sulfuric acids. N-Acetylation predominated at lower doses and O-sulfate conjugation at higher doses. There was no evidence for the formation of N-hydroxylated metabolites over the dose range studied.
在斯普拉格-道利大鼠中研究了[14C]5-氨基-1-萘酚（5A1N）的代谢命运。通过胃插管给雄性大鼠分别给予剂量为1、37和135mg/kg体重的[14C]5A1N。在另一个实验中，大鼠还连续4天每天给予150mg/kg未标记的5A1N。给药剂量的74%至85%经尿液排出。超过98%的尿放射性物质被鉴定为未变化的5A1N、5-乙酰氨基-1-萘酚（5AA1N）以及5A1N和5AA1N的葡萄糖醛酸和硫酸结合物。未变化的5A1N和5AA1N占给药剂量的比例不到3%。5A1N转化为5AA1N及其结合物的量与剂量呈反比。两种次要代谢产物未被鉴定。与单次给药的大鼠相比，重复给予150mg/kg 5A1N的大鼠在代谢产物排泄模式上没有显著变化。这些发现表明，在啮齿动物模型中，5A1N的代谢具有剂量依赖性，主要通过涉及N-乙酰化以及与葡萄糖醛酸和硫酸结合的II相反应发生。低剂量时N-乙酰化占主导，高剂量时O-硫酸结合占主导。在所研究的剂量范围内没有证据表明会形成N-羟基化代谢产物。
