A study of the calcium carbimide-ethanol interaction in man

Abstract

In six male alcoholic volunteers, oral administration of calcium carbimide (0.7 mg/kg) before ingestion of ethanol (0.5 g/kg) produced an interaction consisting of increased blood acetaldehyde level, tachycardia and increased pulse pressure, which was due mainly to decreased diastolic blood pressure. For these experimental conditions, calcium carbimide had a duration of action of at least 24 h to produce an interaction with ethanol. The order of intensity of the interaction with regard to the calcium carbimide pretreatment time interval was 4 greater than 8 approximately 12 greater than 24 h. Using the criterion of heart rate above 100 as indicative of the calcium carbimide-ethanol interaction, the onset was 0.13, 0.25, 0.25 and 0.38 h for the 4-, 8-, 12- and 24-h pretreatment experiments and the duration of the interaction was 1.6, 1.0, 1.0 and 0.12 h, respectively. There were positive linear correlations between acetaldehyde level and heart rate and between acetaldehyde level and pulse pressure. There was appreciable interindividual variability in the heart rate and blood pressure responses. Increased blood acetaldehyde level seemed to be required for the physiological changes to occur. Calcium carbimide pretreatment at the 4-h interval produced increased blood ethanol level for the last hour of the interaction and reduced the rate of ethanol metabolism.

Concentration‐time profiles of ethanol and acetaldehyde in human volunteers treated with the alcohol‐sensitizing drug, calcium carbimide.

“…The combined effect of a smaller distribution volume and a decrease in slope resulted in a statistically significant retardation of ethanol elimination from the body (P < 0.001). This supports the work of Brien et al (1978Brien et al ( , 1979 who investigated the effect of dose of ethanol and time of administration relative to CC pretreatment on the efficacy of the drug-alcohol flush reaction. These workers showed a slower elimination of ethanol when CC was given 4 h before drinking.…”

“…The concentration-time profiles of ethanol and acetaldehyde measured in breath resemble those reported earlier involving direct determinations in specimens of plasma and whole blood (Brien et al, 1978;. Good correlations between breath acetaldehyde and free plasma concentrations were recently demonstrated during the drug-alcohol flush reaction (Stowell et al, 1984).…”

Calcium carbimide–ethanol interaction

“…and there are positive, linear correlations between blood acetaldehyde level and heart rate in individuals for this interaction. 3,4 In view of this it is interesting that for subject 3 the blood acetaldehyde level increased to the greatest extent in experiment 3, with a peak level of 7.94 ILg/ml ( Fig. 2 and Table II), but the heart rate increase was largest in experiment 1, with a peak heart rate of 137 bpm ( Fig.…”

“…3 There is, however, appreciable interindividual variability in the intensity and the duration of the CC-ethanol interaction. :': 4 Because CC has a rapid onset of action (I hr)" it could be administered only when required by the patient, i.e., before a potential drinking situation. Obviously, such an individual must be responsible, motivated, and well aware of typical events that precede drinking situations.…”

Bioavailability of cyanamide in fasted and unfasted rats

“…It interferes with the metabolism of alcohol through non-competitive inhibition of aldehyde dehydrogenase;' increased hepatic and blood acetaldehyde levels result when ethanol has also been ingested. 2 In man the relatively high blood levels of acetaldehyde induce an aversive situation, which appears synchronously with the ingestion of alcohol, it being the alcohol itself which is manifested as a series of unpleasant organic responses e.g. tachycardia, hypotension, facial flushing, that is usually sufficient to deter d r i n k i r~g .~.~ Although the pharmacological activity of cyanamide is well known, there are few references in the literature to its disposition and p h a r m a c o k i n e t i c~.~,~~~ Recently, a pharmacokinetic profile of cyanamide in rat after oral administration of calcium cyanamide was reported by Loomis and Brien,' who showed that the apparent elimination half-life of cyanamide is 92.4 min and that the maximal plasma cyanamide level is achieved 1 hour after oral administration.…”