Renwick A G, Thompson J P, O'Shaughnessy M, Walter E J
Clinical Pharmacology Group, Allergy and Inflammation Research Division, School of Medicine, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.
Toxicol Appl Pharmacol. 2004 May 1;196(3):367-80. doi: 10.1016/j.taap.2004.01.013.
A group of 14 subjects, who had been identified from 261 volunteers in a 1-week screen as being able to metabolize the sweetener cyclamate to cyclohexylamine (>0.2% of a daily dose), and 31 nonconverters (<0.2% metabolism) were given calcium cyclamate tablets (equivalent to 250 mg cyclamic acid, 3 times daily) for a period of 13 weeks. The metabolism of cyclamate to cyclohexylamine was determined using twice-weekly timed (3 h) urine collections during week 1-3 and 7-13. Urine specimens were collected on all other study days to investigate day-to-day fluctuations in cyclohexylamine excretion. Analyses of the twice weekly timed urine collections showed that subjects recruited as nonconverters essentially remained nonconverters. Of the converters, three showed consistently low metabolism, five showed erratic metabolism, five showed low metabolism initially, which increased during the latter part of the study, and one subject showed consistently high metabolism throughout the study. Analysis of the day-to-day urine specimens showed marked intrasubject variability. The plasma concentrations of cyclohexylamine measured on weeks 1-3 and 7-13 reflected the urine profiles. The highest individual long-term average steady-state excretion values based on the 3-h urine collections and daily samples were 21%, 23%, 25%, 29%, 34%, and 38%. The maximum % metabolism detected in the high converters occasionally reached the value of 60% reported in previous short-term studies, but this high activity was not maintained, and was followed by periods of lower metabolism. The results of this metabolism study support an acceptable daily intake (ADI) of 0-11 mg/kg body weight per day.
从261名志愿者中经过1周筛选确定的一组14名受试者，他们能够将甜味剂甜蜜素代谢为环己胺（>每日剂量的0.2%），以及31名非转化者（<0.2%的代谢率），给予他们甜蜜素钙片（相当于250毫克甜蜜酸，每日3次），为期13周。在第1 - 3周和第7 - 13周期间，通过每周两次定时（3小时）收集尿液来测定甜蜜素向环己胺的代谢情况。在所有其他研究日收集尿液样本，以调查环己胺排泄的每日波动情况。对每周两次定时尿液收集的分析表明，招募时被确定为非转化者的受试者基本上仍为非转化者。在转化者中，3人代谢率一直较低，5人代谢不稳定，5人最初代谢率较低，在研究后期有所增加，1名受试者在整个研究过程中代谢率一直较高。对每日尿液样本的分析显示个体内差异显著。在第1 - 3周和第7 - 13周测量的环己胺血浆浓度反映了尿液情况。基于3小时尿液收集和每日样本得出的最高个体长期平均稳态排泄值分别为21%、23%、25%、29%、34%和38%。高转化者中检测到的最大代谢百分比偶尔会达到先前短期研究中报告的60%，但这种高活性并未持续，随后是代谢率较低的时期。这项代谢研究结果支持每日可接受摄入量（ADI）为0 - 11毫克/千克体重。
