Buss N E, Renwick A G, Donaldson K M, George C F
Clinical Pharmacology Group, University of Southampton, Bassett Crescent East, United Kingdom.
Toxicol Appl Pharmacol. 1992 Aug;115(2):199-210. doi: 10.1016/0041-008x(92)90324-l.
A group of 194 diabetic patients were given calcium cyclamate (1 g/day as cyclamic acid equivalents) for a period of 7 days. Blood and urine samples were collected to determine the formation of cyclohexylamine, which is an indirectly acting sympathomimetic amine. Blood pressure and heart rate were recorded before and after treatment. Urine samples were collected each day and analyzed for cyclamate (to check compliance) and cyclohexylamine (to monitor the development of metabolizing activity). After 7 days intake most individuals (78%) did not excrete significant amounts of cyclohexylamine (less than 0.1% of the daily dose of cyclamate) but a small number (8; 4% of the group) excreted more than 20% of the daily dose as cyclohexylamine in the urine. Similar interindividual variations were found in the plasma concentrations of cyclohexylamine after 7 days intake of cyclamate, with 8 individuals having concentrations of 300-1942 ng/ml. The changes in cardiovascular parameters in these 8 subjects between pre- and postdosing were similar to those found in 150 subjects with plasma cyclohexylamine concentrations less than 10 ng/ml. Twenty of the subjects were restudied after receiving calcium cyclamate for 2 weeks at a daily dose equivalent to 2 g of cyclamic acid (0.66 g tds). Plasma concentrations of cyclohexylamine, heart rate, and blood pressure were measured every 30 min for a period of 8 hr (one dose interval) after the final dose. Twelve patients had plasma concentrations of cyclohexylamine greater than 10 ng/ml (89-2043 ng/ml) at the start of the dose-interval investigations. There were no transient increases or decreases in plasma concentrations of cyclohexylamine which might have resulted in a transient change in blood pressure or heart rate. These data indicate that the metabolism of cyclamate (2 g/day) to cyclohexylamine would not affect blood pressure or heart rate even in individuals with high metabolizing ability.
194名糖尿病患者接受甜蜜素钙（以环拉酸当量计为1克/天）治疗7天。采集血液和尿液样本以测定环己胺的形成，环己胺是一种间接作用的拟交感神经胺。记录治疗前后的血压和心率。每天采集尿液样本并分析甜蜜素（以检查依从性）和环己胺（以监测代谢活性的发展）。摄入7天后，大多数个体（78%）未排泄大量环己胺（低于甜蜜素日剂量的0.1%），但少数个体（8名；占该组的4%）在尿液中排泄的环己胺超过日剂量的20%。摄入甜蜜素7天后，环己胺的血浆浓度也发现了类似的个体间差异，8名个体的浓度为300 - 1942纳克/毫升。这8名受试者给药前后心血管参数的变化与150名血浆环己胺浓度低于10纳克/毫升的受试者相似。20名受试者在接受相当于2克环拉酸（0.66克，每日三次）的甜蜜素钙治疗2周后再次接受研究。在最后一剂后8小时（一个给药间隔）内，每30分钟测量一次环己胺的血浆浓度、心率和血压。在给药间隔研究开始时，12名患者的环己胺血浆浓度大于10纳克/毫升（89 - 2043纳克/毫升）。环己胺的血浆浓度没有出现可能导致血压或心率短暂变化的短暂升高或降低。这些数据表明，即使是代谢能力高的个体，甜蜜素（2克/天）代谢为环己胺也不会影响血压或心率。
