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The Use of the Portacaval Transposition Technique to Study Gastrointestinal and Hepatic Metabolism of Propranolol in Dogs

  • M-W. Lo
  • D. J. Effeney
  • S. M. Pond
  • B. M. Silber

Abstract

One of the drugs used extensively to validate the “well- stirred” perfusion model of hepatic drug clearance is propranolol. However, two of the basic assumptions of the model may not be met by propranolol. These are: 1) the liver is the only eliminating organ, and 2) the intrinsic clearance of propranolol is independent of drug concentration entering the liver, and therefore, metabolism is not capacity limited. To test,in vivo, whether or not these assumptions hold when a high first-pass drug such as propranolol is considered, we studied dogs before and after portacaval transposition.

Keywords

Hepatic Metabolism Intrinsic Clearance Perfusion Model Hepatic Drug Clearance American Cyanamid Company 
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References

  1. 1.
    D.J. Effeney, S.M. Pond, M-W. Lo, B.M. Silber and S. Riegelman, A technique to study hepatic and intestinal drug metabolism separately in the dog, J. Pharmacol. Exp. Ther. 221: 507–511 (1982).PubMedGoogle Scholar
  2. 2.
    M-W. Lo and S. Riegelman, Determination of propranolol and its major metabolites in plasma and urine by HPLC without solvent extraction, J. Chromatogr. 183: 213–220 (1980).PubMedCrossRefGoogle Scholar
  3. 3.
    M-W. Lo, D.J. Effeney, S.M. Pond, B.M. Silber and S. Riegelman, Lack of gastrointestinal metabolism of propranolol in dogs after portacaval transposition, J. Pharmacol. Exp. Ther. 221: 512–515 (1982).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • M-W. Lo
    • 1
  • D. J. Effeney
    • 2
  • S. M. Pond
    • 2
  • B. M. Silber
    • 2
  1. 1.Du Pont PharmaceuticalsStine LaboratoryNewarkUSA
  2. 2.Pharmacodynamics Department, Medical Research DivisionAmerican Cyanamid CompanyPearl RiverUSA

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