Studies in detoxication. 22. The metabolism of phenacetin (p-ethoxyacetanilide) in the rabbit and a further observation on acetanilide metabolism.
Studies in detoxication. 22. The metabolism of phenacetin (p-ethoxyacetanilide) in the rabbit and a further observation on acetanilide metabolism.
复制标题
解毒研究。
作者：
J. Smith;R. T. Williams
(1948年7月21日收到)我们已证明乙酰苯胺在1.非那西丁兔的乙基硫酸盐主要转化为对乙酰氨基苯酚的葡萄糖醛酸苷和乙酰尿硫酸盐(Smith&Williams，1948)，其排泄不超过6-7%。(A)检测到含有游离芳香族基团的p-phnetidine化合物。24小时。非那西丁具有解热和镇痛作用，在40-50°~200毫升真空中蒸发。非那西丁在蒸馏液中以异硫氰酸钾的形式存在，与FeCl3类似，呈现类似锰酸盐的颜色，但不能类似的药理性质提示要有足够的分离量进行鉴定。康那西丁可能会产生相同的代谢物，尿液用(NH4)2SO4饱和后再作为乙酰苯胺，本文将用2×200毫升的丙酮提取。丙酮这一说法是正确的。萃取物被分离(离开水层G)，早期的工作人员表明非那西丁导致驯服葡萄糖醛酸脂，见第2(B)(I)节)，中和与增加的乙醚硫酸盐在人，固体K2C08，适合和减少到50毫升。在真空中。狗和兔(Muller，1888；Morner，1889；残留物B用500毫升干丙酮和Baccarani，1900；Hinsberg&Kast，1887；Mahnert，上清层分离并减至50毫升)和Morner分离对乙酰氨基化钾真空。C用乙醚提取，从分离的E-P-RCET-G挥发中提取的8个末端的萃取物产生一个小的油性残留物(D)，颜色试验表明它是从病人的尿液中分离出来的苯乙酸乙酯。D溶于1mL.非那西丁。2-盐酸葡萄糖苷的存在，用稀释的Na2003溶液中和，以及非那西丁中的对氨基酚化合物，用乙醚提取。萃取物被蒸发，人、狗和兔子的尿液也是用这项早期工作建议的少量醋酸酐和稀释液处理的残留物。根据穆勒Na2C03溶液。非那西丁分离和重结晶(1888年)没有不变的非那西丁排出，但从少量热水中，有m.P.和混合m.p.1320M6rner(1889年)发现少量的苯乙替丁(产量，10毫克，或0-07%的剂量)。在人类的尿液中。Hinsberg&Kast(1887)观察到(B)分离对氨基苯酚
(Received 21 July 1948) We have shown thatacetanilide is converted in the 1. The ethereal sulphate fraction of phenacetin rabbit mainly into the glucuronide and ethereal urine sulphate of p-acetamidophenol (Smith & Williams, 1948), not more than 6-7 % being excreted as (a) Detection of free p-ph netidine compounds containing free aromaticamino groups. 24 hr. urine (11.), collected after the feeding of 15 g. Phenacetin has antipyretic and analgesic properties phenacetin, was evaporated in vacuo at 40-50° to 200 ml. Phenetidine was in the distillate by the persimilar to thoeoactaie,utsesstoxc manganate-like colour gives with FeCl3, but could not similar pharmacological properties suggest that be isolated in sufficient amount for identification. The conphenacetin may give rise to the same metabolites centrated urine was saturated with (NH4)2SO4 and then as acetanilide, and in this paper we shall show that extracted with 2 x 200 ml. portions of acetone. The acetone this suggestion is true. extract was separated (leaving an aqueous layer G conEarlier workers showed that phenacetin caused taming glucuronide, see section 2 (b) (i)), neutralized with an increased output of ethereal sulphate in man, the solid K2C08, fitered and reduced to 50 ml. in vacuo. The dog and the rabbit (Muller, 1888; Morner, 1889; residue B was shaken with 500 ml. dry acetone and the Baccarani, 1900; Hinsberg & Kast, 1887; Mahnert, supernatant layer separated and reduced to 50 ml. (C) in 1888) and M orner isolated potassium p-acetamido vacuo. C was now extracted with ether and the extract on 8endls ornate from isolated e p ot pass ium t p rcet g evaporation yielded a small oily residue (D) which appeared phenylsphate from th e urineof patientscreeivi by colour tests to be phenetidine. D was dissolved in 1 ml. phenacetin orally. The presence of a glucuro nide 2-HCI, f fitered, neutralized with dilute Na2003 solution and of compounds of p-aminophenol in phenacetin and extracted with ether. The extract was evaporated, and urine from man, the dog and the rabbit was also the residue treated with a little acetic anhydride and dilute suggested by this early work. According to Muller Na2C03 solution. Phenacetin separated and, recrystallized (1888) no unchanged phenacetin is excreted, but from a little hot water, had m.p. and mixed m.p. 1320 M6rner (1889) found small amounts of phenetidine (yield, 10 mg., or 0-07% of dose). in human urine. Hinsberg & Kast (1887) observed (b) Isolation p-aminophenol