Skip to main content
SpringerLink
Log in

Varying effect of phenobarbital on hepatic drug metabolism in rats of different ages

  • Short Communication
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The developmental pattern of benzo(a)pyrene hydroxylase and ethylmorphine N-demethylase from 8 days before birth up to 100 days of age in rat liver homogenate was investigated. These two drug metabolizing enzyme reactions exhibited their highest activities at different times of hepatic development. Treatment with phenobarbital produces a selective effect on the magnitude of stimulation of these two enzyme reactions in rats of different ages. The higher levels of drug metabolizing enzyme activity after phenobarbital treatment were not always paralleled by higher liver weights. The duration of hexobarbital hypnosis was longer in young than in adult rats. However, after phenobarbital treatment hexobarbital effectiveness was decreased more in young than in adult rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Basu, T. K., Dickerson, J. W. T., Parke, D. V. W.: Effect of development on the activity of microsomal drug metabolizing enzymes in rat liver. Biochem. J. 124, 19–24 (1971)

    Google Scholar 

  • Borowski, R.: Personal communication (1973)

  • Conney, A. H., Levin, W., Jacobson, M., Kuntzman, R., Cooper, D. H., Rosenthal, O.: Specificity in the regulation of the 6β-, 7α- and 16α-hydroxylation of testosterone by rat liver microsomes. In: Microsomes and drug oxidations, pp. 279–302, J. R. Gillette, A. H. Conney, G. J. Cosmides, R. W. Estabrook, J. R. Fouts, and G. J. Mannering, Eds.. New York-London: Academic Press 1969

    Google Scholar 

  • Conney, A. H., Lu, A. Y. H., Levin, W., Somogyi, A., West, S., Jacobson M., Ryan, D., Kuntzman, R.: Effect of enzyme inducers on substrate specificity of the cytochrome P-450's. Drug metabolism and Disposition 1, 199–210 (1973)

    Google Scholar 

  • Dallner, G., Siekevitz, P., Palade, G. E.: Biogenesis of endoplasmic reticulum membranes. I. Structural and chemical differentiation in developing rat hepatocyte. J. Cell Biol. 30, 73–96 (1966)

    Google Scholar 

  • Dallner, G., Siekevitz, P., Palade, G. E.: Biogenesis of endoplasmic reticulum membranes. II. Synthesis of constitutive microsomal enzymes in developing rat hepatocyte. J. Cell Biol. 30, 97–117 (1966)

    Google Scholar 

  • Gram, Th. E., Guarino, A. M., Schroeder, D. H., Gillette, J. R.: Changes in certain kinetic properties of hepatic microsomal aniline hydroxylase and ethylmorphine demethylase with postnatal development and maturation in male rats. Biochem. J. 113, 681–685 (1969)

    Google Scholar 

  • Henderson, P. Th.: Metabolism of drugs in rat liver during the perinatal period. Biochem. Pharmacol. 20, 1225–1232 (1971)

    Google Scholar 

  • Kato, R., Takanaka, A.: Effect of phenobarbital on electron transport system, oxidation and reduction of drugs in liver microsomes of rats of different ages. J. Biochem. 63, 406–408 (1968)

    Google Scholar 

  • Kato, R., Vasanelli, P., Frontino, G., Chiesara, E.: Variation of the activity of liver microsomal drug metabolizing enzymes in rats in relation to the age. Biochem. Pharmacol. 13, 1037–1051 (1964)

    Google Scholar 

  • Kuntzman, R., Mark, L. C., Brand, L., Jacobson, M., Levin, W., Conney, A. H.: Metabolism of drugs and carcinogens by human liver enzymes. J. Pharmacol. exp. Ther. 152, 151–156 (1966)

    Google Scholar 

  • Nash, T.: The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem. J. 55, 416–421 (1953)

    Google Scholar 

  • Schlede, E., Borowski, R.: Decreased effect of phenobarbital treatment on drug metabolizing enzyme activity during gestation. Naunyn-Schmiedeberg's Arch. Pharmacol. 281, 341–355 (1974)

    Google Scholar 

  • Schlede, E., Merker, H.-J.: Effect of benzo(α)pyrene treatment on the benzo(α)-pyrene hydroxylase activity in maternal liver, placenta and fetus of the rat during day 13 to day 18 of gestation. Naunyn-Schmiedberg's Arch. Pharmacol. 272, 89–100 (1972)

    Google Scholar 

  • Wattenberg, L. M., Leong, J. L., Strand, P. J.: Benzpyrene hydroxylase activity in the gastrointestinal tract. Cancer Res. 22, 1120–1125 (1962)

    Google Scholar 

  • Welch, R. M., Gommi, B., Alvares, A. P., Conney, A. H.: Effect of enzyme induction on the metabolism of benzo(a)pyrene and 3′-methyl-4-monomethylaminoazobenzene in the pregnant and fetal rat. Cancer Res. 32, 973–978 (1972)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Pharmakologie der Freien Universität Berlin, Berlin, Germany

    Eva Schlede

Authors
  1. Eva Schlede
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schlede, E. Varying effect of phenobarbital on hepatic drug metabolism in rats of different ages. Naunyn-Schmiedeberg's Arch. Pharmacol. 282, 311–315 (1974). https://doi.org/10.1007/BF00501239

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00501239

Key words

Search

Navigation