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. 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)

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Selected References

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  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]

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