Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1988 Feb;25(2):213–221. doi: 10.1111/j.1365-2125.1988.tb03293.x

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

A W Jones 1, J Neiman 1, M Hillbom 1
PMCID: PMC1386476  PMID: 3358883

Abstract

1. The disposition kinetics of ethanol and its toxic metabolite acetaldehyde were investigated in 10 healthy male volunteers who ingested 0.25 g kg-1 ethanol after an overnight fast. This dose of ethanol was given 2 h after they swallowed a tablet of either calcium carbimide CC (50 mg), a potent inhibitor of low Km aldehyde dehydrogenase (ALDH), or placebo according to a single-blind crossover design. 2. The pulmonary blood concentrations of ethanol and acetaldehyde were estimated indirectly by means of a gas chromatographic method modified for analysis of end-expired breath. This non-invasive sampling technique allowed replicate determinations at 15 min intervals. 3. The distribution volume of ethanol (V) was 0.64 +/- 0.023 1 kg-1 after CC and 0.68 +/- 0.026 l kg-1 after placebo treatment (P greater than 0.05). The zero order slope of the blood-ethanol decay profile (ko) decreased by about 5% when low Km ALDH was inhibited. The elimination of ethanol from the body (V X ko) was 1.9 +/- 0.051 mmol kg-1 h-1 after CC compared with 2.11 +/- 0.056 mmol kg-1 h-1 in placebo control experiments (P less than 0.001). The area under the ethanol concentration time curve (0----180 min) increased after CC treatment implying a change in clearance. 4. The disposition of acetaldehyde was markedly different in subjects pretreated with CC. The peak blood-concentrations, estimated by analysis of breath, ranged from 40-242 mumol l-1 compared with 1.7-6.5 mumol l-1 after placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
215

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brien J. F., Peachey J. E., Loomis C. W., Rogers B. J. The calcium carbimide-ethanol interaction: effects of ethanol dose. Clin Pharmacol Ther. 1979 Apr;25(4):454–463. doi: 10.1002/cpt1979254454. [DOI] [PubMed] [Google Scholar]
  2. Brien J. F., Peachey J. E., Rogers B. J., Loomis C. W. A study of the calcium carbimide-ethanol interaction in man. Eur J Clin Pharmacol. 1978 Nov 16;14(2):133–141. doi: 10.1007/BF00607445. [DOI] [PubMed] [Google Scholar]
  3. Cronholm T. Hydrogen transfer between ethanol molecules during oxidoreduction in vivo. Biochem J. 1985 Jul 15;229(2):315–322. doi: 10.1042/bj2290315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ikawa M., Impraim C. C., Wang G., Yoshida A. Isolation and characterization of aldehyde dehydrogenase isozymes from usual and atypical human livers. J Biol Chem. 1983 May 25;258(10):6282–6287. [PubMed] [Google Scholar]
  5. Jauhonen P., Baraona E., Miyakawa H., Lieber C. S. Origin of breath acetaldehyde during ethanol oxidation. Effect of long-term cigarette smoking. J Lab Clin Med. 1982 Dec;100(6):908–916. [PubMed] [Google Scholar]
  6. Jones A. W. Determination of liquid/air partition coefficients for dilute solutions of ethanol in water, whole blood, and plasma. J Anal Toxicol. 1983 Jul-Aug;7(4):193–197. doi: 10.1093/jat/7.4.193. [DOI] [PubMed] [Google Scholar]
  7. Jones A. W. Excretion of low-molecular weight volatile substances in human breath: focus on endogenous ethanol. J Anal Toxicol. 1985 Nov-Dec;9(6):246–250. doi: 10.1093/jat/9.6.246. [DOI] [PubMed] [Google Scholar]
  8. Jones A. W. Interindividual variations in the disposition and metabolism of ethanol in healthy men. Alcohol. 1984 Sep-Oct;1(5):385–391. doi: 10.1016/0741-8329(84)90008-9. [DOI] [PubMed] [Google Scholar]
  9. Jones A. W. Quantitative measurements of the alcohol concentration and the temperature of breath during a prolonged exhalation. Acta Physiol Scand. 1982 Mar;114(3):407–412. doi: 10.1111/j.1748-1716.1982.tb07002.x. [DOI] [PubMed] [Google Scholar]
  10. Jones A. W., Sato A., Forsander O. A. Liquid/air partition coefficients of acetaldehyde: values and limitations in estimating blood concentrations from analysis of breath. Alcohol Clin Exp Res. 1985 Sep-Oct;9(5):461–464. doi: 10.1111/j.1530-0277.1985.tb05583.x. [DOI] [PubMed] [Google Scholar]
  11. Jones A. W., Skagerberg S., Borg S., Anggård E. Time course of breath acetaldehyde concentrations during intravenous infusions of ethanol in healthy men. Drug Alcohol Depend. 1984 Oct;14(2):113–119. doi: 10.1016/0376-8716(84)90036-x. [DOI] [PubMed] [Google Scholar]
  12. Lindros K. O., Stowell A., Pikkarainen P., Salaspuro M. The disulfiram (Antabuse)-Alcohol reaction in male alcoholics: its efficient management by 4-methylpyrazole. Alcohol Clin Exp Res. 1981 Fall;5(4):528–530. doi: 10.1111/j.1530-0277.1981.tb05354.x. [DOI] [PubMed] [Google Scholar]
  13. Lundquist F. Acetaldehyde and aldehyde dehydrogenases--central problems in the study of alcoholism. Eur J Clin Invest. 1983 Jun;13(3):183–184. doi: 10.1111/j.1365-2362.1983.tb00085.x. [DOI] [PubMed] [Google Scholar]
  14. Mizoi Y., Ijiri I., Tatsuno Y., Kijima T., Fujiwara S., Adachi J., Hishida S. Relationship between facial flushing and blood acetaldehyde levels after alcohol intake. Pharmacol Biochem Behav. 1979 Feb;10(2):303–311. doi: 10.1016/0091-3057(79)90105-9. [DOI] [PubMed] [Google Scholar]
  15. Nuutinen H. U., Salaspuro M. P., Valle M., Lindros K. O. Blood acetaldehyde concentration gradient between hepatic and antecubital venous blood in ethanol-intoxicated alcoholics and controls. Eur J Clin Invest. 1984 Aug;14(4):306–311. doi: 10.1111/j.1365-2362.1984.tb01186.x. [DOI] [PubMed] [Google Scholar]
  16. Nuutinen H., Lindros K. O., Salaspuro M. Determinants of blood acetaldehyde level during ethanol oxidation in chronic alcoholics. Alcohol Clin Exp Res. 1983 Spring;7(2):163–168. doi: 10.1111/j.1530-0277.1983.tb05432.x. [DOI] [PubMed] [Google Scholar]
  17. Peachey J. E., Brien J. F., Roach C. A., Loomis C. W. A comparative review of the pharmacological and toxicological properties of disulfiram and calcium carbimide. J Clin Psychopharmacol. 1981 Jan;1(1):21–26. doi: 10.1097/00004714-198101000-00005. [DOI] [PubMed] [Google Scholar]
  18. Peachey J. E., Sellers E. M. The disulfiram and calcium carbimide acetaldehyde-mediated ethanol reactions. Pharmacol Ther. 1981;15(1):89–97. doi: 10.1016/0163-7258(81)90018-8. [DOI] [PubMed] [Google Scholar]
  19. Pikkarainen P. H., Baraona E., Jauhonen P., Seitz H. K., Lieber C. S. Contribution of oropharynx microflora and of lung microsomes to acetaldehyde in expired air after alcohol ingestion. J Lab Clin Med. 1981 May;97(5):631–636. [PubMed] [Google Scholar]
  20. Sellers E. M., Naranjo C. A., Peachey J. E. Drug therapy: Drugs to decrease alcohol consumption. N Engl J Med. 1981 Nov 19;305(21):1255–1262. doi: 10.1056/NEJM198111193052105. [DOI] [PubMed] [Google Scholar]
  21. Stowell A., Johnsen J., Aune H., Vatne K., Ripel A., Mørland J. A reinvestigation of the usefulness of breath analysis in the determination of blood acetaldehyde concentrations. Alcohol Clin Exp Res. 1984 Sep-Oct;8(5):442–447. doi: 10.1111/j.1530-0277.1984.tb05698.x. [DOI] [PubMed] [Google Scholar]
  22. Yoshida A., Davé V. Enzymatic activity of atypical Oriental types of aldehyde dehydrogenases. Biochem Genet. 1985 Aug;23(7-8):585–590. doi: 10.1007/BF00504292. [DOI] [PubMed] [Google Scholar]
  23. von Wartburg J. P., Bühler R. Biology of disease. Alcoholism and aldehydism: new biomedical concepts. Lab Invest. 1984 Jan;50(1):5–15. [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES