Caldwell J, Sutton J D
Department of Pharmacology and Toxicology, St Mary's Hospital Medical School, London, England.
Food Chem Toxicol. 1988 Feb;26(2):87-91. doi: 10.1016/0278-6915(88)90103-2.
The influence of dose size on the metabolic fate of the naturally occurring food flavouring trans-anethole has been investigated in human volunteers, using the [methoxy-14C]-labelled compound. The doses chosen were: 1 mg; close to the daily intake in the diet from foods, 50 mg; approximating to the amount present in a normal measure of an anise-flavoured beverage, and 250 mg. The order of administration was randomized. The major routes of elimination of 14C were in the urine (54-69% of the administered dose) and as exhaled 14CO2 (13-17%). Dose size had no systematic effect on either rate or route of excretion. Urinary metabolites were separated by high-pressure liquid chromatography, before and after treatment with beta-glucuronidase, and identified by comparison of their chromatographic mobilities with those of authentic standards. The principal metabolite (greater than 90% of urinary 14C) was 4-methoxyhippuric acid, accompanied by much smaller amounts of 4-methoxybenzoic acid and up to three other compounds, which were not examined further. The pattern of urinary metabolites was unaffected by dose size. These data are discussed with reference to the comparative metabolic disposition of trans-anethole in rats and mice, the species commonly used in toxicity testing and in which its fate exhibits a very marked dose dependence.
利用[甲氧基 - ¹⁴C]标记的化合物，在人类志愿者中研究了剂量大小对天然存在的食用香料反式茴香脑代谢命运的影响。所选择的剂量分别为：1毫克，接近日常饮食中从食物摄入的量；50毫克，近似于一份正常量茴芹味饮料中的含量；以及250毫克。给药顺序是随机的。¹⁴C的主要消除途径是通过尿液（占给药剂量的54 - 69%）和呼出的¹⁴CO₂（13 - 17%）。剂量大小对排泄速率或途径均无系统性影响。在用β - 葡萄糖醛酸酶处理前后，通过高压液相色谱法分离尿液代谢物，并通过将其色谱迁移率与真实标准品的迁移率进行比较来鉴定。主要代谢物（占尿液¹⁴C的90%以上）是4 - 甲氧基马尿酸，同时伴有少量的4 - 甲氧基苯甲酸和多达三种其他未进一步研究的化合物。尿液代谢物的模式不受剂量大小的影响。结合反式茴香脑在大鼠和小鼠（毒性测试中常用的物种，其代谢命运表现出非常明显的剂量依赖性）中的比较代谢情况对这些数据进行了讨论。
