Summary
Tissue distribution of disulfiram in the rat was studied after a single dose and after repeated daily administration for a one-month period.
After the single dose, disulfiram was found in dose-related quantities in the blood, liver, kidney, spleen, brain, muscle and peri-epididymal adipose tissue. After one-month treatment accumulation of the product was found to be unrelated to the dose, suggesting a saturation point for the various organs. After the treatment was stopped, the disulfiram level gradually decreased, reaching zero value only after 14 days. The results seem to indicate that the product remains in the organs and tissues in significant quantities for as long as two weeks.
Resume
La localisation tissulaire du disulfirame a été étudiée chez le Rat traité avecune seule dose, ou quotidiennement pendant un mois; lors du traitement aigu, le disulfirame se retrouve en quantités proportionnelles à la dose dans le sang, le foie, le rein, la rate et le cerveau et on en retrouve aussi dans le muscle et le tissu adipeux péri-épididymaire. Après un traitement d’un mois, le stockage tissulaire est indépendant de la dose, comme si les différents organes s’étaient chargés de disulfirame jusqu’à saturation. Lorsque le traitement chronique est arrêté, le taux de disulfirame régresse lentement et ne devient nul qu’au bout de 14 jours. II est conclu que le disulfirame est fixe d’une manière stable sur diverses structures endogènes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Hald J., Jacobsen E. and Larsen V. (1948): The sensitizing effect of tetraethylthiouram disulfide to ethyl alcohol. Acta. Pharmacol. Toxicol.,4, 285–296.
Saint-Blanquat de G. and Derache R. (1976): Mecanisme d’action des substances anti-alcool dependantes (disulfirame). J. Pharmacol. (Paris),7, 393–408.
Kitson T.M. (1977): The disulfiram-ethanol Reaction. A review. J. Stud. Alcohol,38, 96–113.
Kjeldgaard N.O. (1949): Inhibition of aldehyde oxidase from liver by tetraethylthiouram disulphide (Antabuse). Acta Pharmacol. Toxicol.,5, 397–403.
Goldstein M., Anagnoste B., Lauber E. and McKereghan M.R. (1964): Inhibition of dopamine β-hydroxylase by disulfiram. Life Sci.,3, 763–767.
Rahwan R.G. (1974): Speculation on the biochemical pharmacology of ethanol. Life Sci.,15, 617–633.
Saint-Blanquat G. de, Vidaillac G., Lindenbaum A. and Derache R. (1976): Absorption digestive, fixation tissulaire et excrétion du disulfirame administré oralement chez le rat. Arch. Int. Pharmacodyn. Ther.,223, 339–350.
Vidaillac G., Saint-Blanquat G. de and Derache R. (1978): Fixation tissulaire du35s disulfirame chez le Rat (à paraître).
Asmussen E., Hald J., Jacobsen E. and Jorgensen G. (1948): Studies on the effect of tetraethylthiouram disulfide (antabuse) and alcohol on respiration and circulation in normal subjects. Acta Pharmacol.,4, 297–304.
Lang M., Marselos M. and Torronen R. (1976): Modifications of drug metabolism by disulfiram and diethyldithiocarbamate. Chem. Biol. Interractions,15, 267–276.
Royer R.J., Marquis P., Morrot M.J. and Alexandre P. (1974): Effet thrombopéniant du disulfirame chez le lapin. Compt. Rend. Soc. Biol.,168, 1054–1056.
Royer R.J., Lamarche M., Humbert F. and Gay G. (1972): Variation chez le lapin, des valeurs de la 5-hydroxy-tryptamine de la rate, du cerveau, de l’intestin grêle et du gros intestin sous l’influence du disulfirame. Compt. Rend. Soc. Biol.,166, 193–195.
Strömme J.H. (1965): Interractions of disulfiram and diethyldithiocarbamate with serum proteins studied by means of a gel filtration technique. Biochem. Pharmacol.,14, 381–391.
Butler M., Giannina T., Cardill D.I., Popick F. and Steinetz B.G. (1969): Abnormal sulfhydryl-disulfide interchange in serum of rats with adjuvant arthritis: correction by anti-inflammatory agents. Exp. Biol. Med.,132, 484–488.
Norseth T. (1974): Effect of diethyldithiocarbamate on biliary transport, excretion and organ distribution of mercury in the rat after exposure to methylmercuric chloride. Acta Pharmacol. Toxicol.,34, 76–87.
Iwalon H., Watanabe K., Müchi H. and Matoni Y. (1970): Accumulation of copper in the central nervous system on prolonged administration of Na DDC to rats. Pharmacol. Res. Commun.,2, 213–220.
Strömme J.H. (1965): Metabolism of disulfiram and diethyldithiocarbamate in rats with demonstration of an in vivo ethanol-induced inhibition of the glucuronic acid conjunction of the thiol. Biochem. Pharmacol.,14, 393–410.
Gessner T. and Jakubowski M. (1972): Diethyldithiocarbimic acid methyl ester: a metabolite of disulfiram. Biochem. Pharmacol.,21, 219–230.
Merlevede E. et Casier H. (1961): Teneur en sulfure de carbone de l’air expiré chez des personnes normales ou sous rinfluence de l’alcool éthylique au cours de traitement par l’Antabuse et le diéthyldithiocarbamate de soude. Arch. Int. Pharmacodyn.,132, 427–453.
Raskin N.H. and Sokoloff L. (1972): Ethanol induced adaptation of alcohol dehydrogenase activity in rat brain. Nature New Biology,236, 138–140.
Deitrich R.A. and Erwin V.G. (1971): Mechanism of the inhibition of aldehyde dehydrogenase in vivo by disulfiram and diethyldithiocarbamate. Molecular Pharmacol.7, 301–307.
Izquierdo J.A., Joffre I.J. and Acevedo C. (1972): Effect of disulfiram and ascorbic acid on catecholamine content in rat brain. J. Pharm. Pharmacol.,24, 330–332.
Labianca D.A. (1974): Acetaldehyde syndrome and alcoholism. Chemistry,47, 21.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
De Saint-Blanquat, G., Vidaillac, G. & Lamboeuf, Y. Stockage et liberation tissulaires du disulfirame administre de diverses façons chez le rat. European Journal of Drug Metabolism and Pharmacokinetics 3, 205–209 (1978). https://doi.org/10.1007/BF03189385
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF03189385