The metabolism of cyclamate to cyclohexylamine and its cardiovascular consequences in human volunteers.
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.
Buss
N E
NE
Clinical Pharmacology Group, University of Southampton, Bassett Crescent East, United Kingdom.
Renwick
A G
AG
Donaldson
K M
KM
George
C F
CF
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D003404:Creatinine / Q000652:urine; D003494:Cyclamates / Q000378:metabolism* / Q000494:pharmacology; D003514:Cyclohexylamines / Q000097:blood* / Q000652:urine; D003920:Diabetes Mellitus / Q000378:metabolism; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013549:Sweetening Agents / Q000378:metabolism* / Q000494:pharmacology; D013607:Tablets
D003494:Cyclamates; D003514:Cyclohexylamines; D013549:Sweetening Agents; D013607:Tablets; D003404:Creatinine