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[甲氧基-14C]标记的反式茴香脑、草蒿脑和对丙基茴香醚在人体志愿者体内的代谢情况。

The metabolic disposition of [methoxy-14C]-labelled trans-anethole, estragole and p-propylanisole in human volunteers.

作者信息

Sangster S A, Caldwell J, Hutt A J, Anthony A, Smith R L

机构信息

Department of Pharmacology, St. Mary's Hospital Medical School, London, England.

出版信息

Xenobiotica. 1987 Oct;17(10):1223-32. doi: 10.3109/00498258709167414.

DOI:10.3109/00498258709167414
PMID:3424869
Abstract
  1. The metabolic fates of the naturally occurring food flavours trans-anethole and estragole, and their synthetic congener p-propylanisole, have been investigated in human volunteers using the [methoxy-14C]-labelled compounds. The doses used were close to those encountered in the diet, 1 mg, 100 micrograms and 100 micrograms respectively. 2. In each case, the major routes of elimination of 14C were in the urine and in the expired air as 14CO2. 3. Urinary metabolites were separated by solvent extraction, t.l.c. and h.p.l.c., and characterized by comparison of chromatographic mobilities with standards and by radioisotope dilution. Nine 14C urinary metabolites were found after trans-anethole administration, four after p-propylanisole and five after estragole. All were products of side chain oxidations. 4. The principal metabolites of p-propylanisole were 4-methoxyhippuric acid (12%) and 1-(4'-methoxyphenyl)propan-1-ol (2%) and -2-ol (8%). 5. The major metabolite of trans-anethole was 4-methoxyhippuric acid (56% of dose), accompanied by much smaller amounts of the two isomers of 1-(4'-methoxyphenyl)propane-1,2-diol (together 3%). 6. After estragole administration, the two volunteers eliminated 0.2 and 0.4% of the dose respectively as 1'-hydroxyestragole. 7. The human metabolic data is discussed with reference to the comparative metabolic disposition of these compounds in the mouse and rat, species commonly used in their safety assessment.
摘要
  1. 利用[甲氧基 - ¹⁴C]标记的化合物,在人类志愿者中研究了天然存在的食用香料反式茴香脑和草蒿脑及其合成类似物对丙基苯甲醚的代谢命运。所使用的剂量分别接近饮食中所摄入的剂量,即1毫克、100微克和100微克。2. 在每种情况下,¹⁴C的主要消除途径是通过尿液和呼出的¹⁴CO₂。3. 通过溶剂萃取、薄层层析和高效液相色谱法分离尿液代谢物,并通过与标准品的色谱迁移率比较和放射性同位素稀释法进行表征。给予反式茴香脑后发现了9种¹⁴C尿液代谢物,给予对丙基苯甲醚后发现了4种,给予草蒿脑后发现了5种。所有这些都是侧链氧化的产物。4. 对丙基苯甲醚的主要代谢物是4 - 甲氧基马尿酸(12%)、1 - (4'-甲氧基苯基)丙 - 1 - 醇(2%)和 - 2 - 醇(8%)。5. 反式茴香脑的主要代谢物是4 - 甲氧基马尿酸(占剂量的56%),同时伴有少量的1 - (4'-甲氧基苯基)丙烷 - 1,2 - 二醇的两种异构体(总计3%)。6. 给予草蒿脑后,两名志愿者分别以1'-羟基草蒿脑的形式消除了剂量的0.2%和0.4%。7. 参照这些化合物在小鼠和大鼠(常用于其安全性评估的物种)中的比较代谢情况,讨论了人类代谢数据。

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The metabolic disposition of [methoxy-14C]-labelled trans-anethole, estragole and p-propylanisole in human volunteers.[甲氧基-14C]标记的反式茴香脑、草蒿脑和对丙基茴香醚在人体志愿者体内的代谢情况。
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