European Journal of Clinical Pharmacology

, Volume 11, Issue 5, pp 337–344

The kinetics of ethanol absorption and elimination in twins and supplementary repetitive experiments in singleton subjects

  • M. Kopun
  • P. Propping
Originals

Summary

The influence of genetic and environmental factors on the metabolism of a single oral dose of ethanol 1.2 ml per kg body weight was analysed in 19 identical and 21 fraternal healthy, adult, un-selected male twin pairs. The heritability values of the rates of absorption, degradation and elimination of ethanol were 0.57, 0.41 and 0.46 respectively. Environmental factors, such as daily alcohol intake and smoking, increased the rate of elimination of blood alcohol. Intrasubject variation in ethanol metabolism was studied by repeated tests in 11 male volunteers at intervals of at least 2 months, under the same conditions as in the twins; the coefficients of variation for parameters of metabolism was about 8%. The results demonstrate both genetic control of ethanol absorption, degradation and elimination and the appreciable influence of environmental factors. The almost total genetic control of ethanol metabolism postulated by Vesell et al. (1971) could not be confirmed.

Key words

Twin study ethanol metabolism intra-individual variation pharmacogenetics plasma level man heritability 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Begleiter, H., Platz, A.: The effects of alcohol on the central nervous system in humans. In: The Biology of Alcoholism (ed. Kissin, H., Begleiter, H.), Vol. 2, pp. 293–343. New York, London: Plenum Press 1972Google Scholar
  2. Bücher, T., Redetzki, H.: Eine spezifische photometrische Bestimmung von Äthylalkohol auf fermentativem Wege. Klin. Wschr.29, 615–616 (1951)Google Scholar
  3. Elbel, H., Schleyer, F.: Blutalkohol. Die wissenschaftlichen Grundlagen der Beurteilung von Blutalkoholbefinden bei Straßenverkehrsdelikten, 2nd ed. Stuttgart: Georg Thieme 1956Google Scholar
  4. Ekman, G., Frankenhaeuser, M., Goldberg, L., Bjerver, K., Järpe, G., Myrsten, A.-L.: Effects of alcohol intake on subjective and objective variables over a five-hour period. Psychopharmacologia (Berl.)4, 28–38 (1963)Google Scholar
  5. Ekman, G., Frankenhaeuser, M., Goldberg, L., Hagdahl, R., Myrsten, A.-L.: Subjective and objective effects of alcohol as functions of dosage and time. Psychopharmacologia (Berl.)6, 399–409 (1964)Google Scholar
  6. Goldberg, L.: Quantitative studies on alcohol tolerance in man. Acta physiol. scand.5, Suppl. 16, 1–128 (1943)Google Scholar
  7. Goldberg, L.: Behavioral and physiological effects of alcohol in man. Psychosom. Med.28, 570–595 (1966)Google Scholar
  8. Ideström, C.-M., Cadenius, B.: Time relations of the effects of alcohol compared to placebo. Dose-response curves for psychomotor and perceptual test performances and blood and urine levels of alcohol. Psychopharmacologia (Berl.)13, 189–200 (1968)Google Scholar
  9. Kalant, H.: Absorption, diffusion, distribution, and elimination of ethanol: Effects on biological membranes. In: The Biology of Alcoholism (ed. Kissin, H., Begleiter, H.) Vol. 1, pp. 1–62. New York, London: Plenum Press 1971Google Scholar
  10. Lieber, C.S., DeCarli, L.M.: Ethanol oxidation by hepatic microsomes: Adaptive increase after ethanol feeding. Science162, 917–918 (1968)Google Scholar
  11. Lieber, C.S., DeCarli, L.M.: Hepatic microsomal ethanol-oxidizing system. In vitro characteristics and adaptive properties in vivo. J. biol. Chem.245, 2505–2512 (1970)Google Scholar
  12. Lüth, K.-F.: Untersuchungen über die Alkoholblutkonzentration nach Alkoholgaben bei 10 eineiigen und 10 zweieiigen Zwillingspaaren. Dtsch. Z. gerichtl. Med.32, 145–164 (1939)Google Scholar
  13. Propping, P.: Genetic control of ethanol action on the central nervous system. An EEG study in twins. Human. Genet. in press, (1977)Google Scholar
  14. Sidell, F.R., Pless, J.E.: Ethyl alcohol: blood levels and performance decrements after oral administration to man. Psychopharmacologia (Berl.)19, 246–261 (1971)Google Scholar
  15. Thieden, H.I.D.: Ethanol metabolism in the liver. Acta pharmacol. toxicol.36, suppl. I, 1–51 (1975)Google Scholar
  16. Vesell, E.S., Page, J.G., Passananti, G.T.: Genetic and environmental factors affecting ethanol metabolism in man. Clin. Pharmacol. Ther.12, 192–201 (1971)Google Scholar
  17. Vogel, F.: Lehrbuch der allgemeinen Humangenetik. Berlin, Göttingen, Heidelberg: Springer 1961Google Scholar
  18. Wagner, J.G.: Properties of the Michaelis-Menten equations and its integrated form which are useful in pharmacokinetics. J. Pharmacokin. Biopharm.1, 103–121 (1973a)Google Scholar
  19. Wagner, J.G.: Intrasubject variation in elimination half-lives of drugs which are appreciably metabolized. J. Pharmacokin. Biopharm.1, 165–173 (1973b)Google Scholar
  20. Wagner, J.G., Patel, J.A.: Variations in absorption and elimination rates of ethyl alcohol in a single subject. Res. Com. chem. Pathol. Pharmacol.4, 61–76 (1972)Google Scholar
  21. Wagner, J.G., Wilkinson, P.K., Sedman, A.J., Kay, D.R., Weidler, D.J.: Elimination of alcohol from human blood. J. Pharm. Sci.65, 152–154 (1976)Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • M. Kopun
    • 1
  • P. Propping
    • 1
  1. 1.Institut für Anthropologie und HumangenetikUniversität HeidelbergHeidelbergFederal Republic of Germany
  2. 2.Institut für Zellforschung am Deutschen KrebsforschungszentrumHeidelbergFederal Republic of Germany

Personalised recommendations