The metabolic fate of amphetamine in man and other species.
The metabolic fate of amphetamine in man and other species.
复制标题
安非他明在人类和其他物种中的代谢命运。
作者：
L. Dring;Richard L. Smith;R. T. Williams
1.研究了[（14）C]苯丙胺在人、恒河猴、灰狗、大鼠、兔、小鼠和豚鼠体内的归趋。2.在三名男性中，每人口服5 mg（约0.07mg/kg），约90%的（14）C在3-4天内从尿中排出。约60-65%的（14）C在1天内排出，其中30%以原型药物形式排出，21%以总苯甲酸形式排出，3%以4-羟基苯丙胺形式排出。3.在两只恒河猴（剂量为0.66mg/kg）中，24小时内排泄的代谢物与人相似，但几乎没有4-羟基苯丙胺。4.灰狗腹腔注射5 mg/kg，代谢物的量与人相似。接受10 mg/kg经口给药的家兔与所有其他种属不同。它们几乎不排泄原型苯丙胺（剂量的4%）和4-羟基苯丙胺（6%）。它们在24 h内主要排泄苯甲酸（总计25%）、1-苯基丙-2-酮（苄基甲基酮）的酸不稳定前体（22%）和共轭1-苯基丙-2-醇（苄基甲基甲醇）（7%）。6.经口给予10 mg/kg的大鼠也与其他物种不同。主要代谢产物（剂量的60%）为结合4-羟基苯丙胺。次要代谢物为苯丙胺（13%）、N-乙酰苯丙胺（2%）、去甲麻黄碱（0.3%）和4-羟基去甲麻黄碱（0.3%）。7.接受5 mg/kg的豚鼠仅排泄苯甲酸及其结合物（62%）和苯丙胺（22%）。8.接受10 mg/kg的小鼠排泄苯丙胺（33%）、4-羟基苯丙胺（14%）和苯甲酸及其结合物（31%）。9.对兔尿中1-苯丙-2-酮前体的实验表明，它可能是酮的烯醇硫酸盐。在酸水解后，在人和灰狗尿液中也发现了极少量的酮（1-3%）。
1. The fate of [(14)C]amphetamine in man, rhesus monkey, greyhound, rat, rabbit, mouse and guinea pig has been studied. 2. In three men receiving orally 5mg each (about 0.07mg/kg), about 90% of the (14)C was excreted in the urine in 3-4 days. About 60-65% of the (14)C was excreted in 1 day, 30% as unchanged drug, 21% as total benzoic acid and 3% as 4-hydroxyamphetamine. 3. In two rhesus monkeys (dose 0.66mg/kg), the metabolites excreted in 24h were similar to those in man except that there was little 4-hydroxyamphetamine. 4. In greyhounds receiving 5mg/kg intraperitoneally the metabolites were similar in amount to those in man. 5. Rabbits receiving 10mg/kg orally differed from all other species. They excreted little unchanged amphetamine (4% of dose) and 4-hydroxyamphetamine (6%). They excreted in 24h mainly benzoic acid (total 25%), an acid-labile precursor of 1-phenylpropan-2-one (benzyl methyl ketone) (22%) and conjugated 1-phenylpropan-2-ol (benzylmethylcarbinol) (7%). 6. Rats receiving 10mg/kg orally also differed from other species. The main metabolite (60% of dose) was conjugated 4-hydroxyamphetamine. Minor metabolites were amphetamine (13%), N-acetylamphetamine (2%), norephedrine (0.3%) and 4-hydroxynorephedrine (0.3%). 7. The guinea pig receiving 5mg/kg excreted only benzoic acid and its conjugates (62%) and amphetamine (22%). 8. The mouse receiving 10mg/kg excreted amphetamine (33%), 4-hydroxyamphetamine (14%) and benzoic acid and its conjugates (31%). 9. Experiments on the precursor of 1-phenylpropan-2-one occurring in rabbit urine suggest that it might be the enol sulphate of the ketone. A very small amount of the ketone (1-3%) was also found in human and greyhound urine after acid hydrolysis.