, Volume 1, Issue 4, pp 264-279
Date: 15 Dec 2012

Propranolol Disposition in Chronic Liver Disease: A Physiological Approach

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Summary

The pharmacokinetics of propranolol can be quantitatively explained on a physiological basis from a knowledge of the effects of four biological determinants: (1) the activity of the drug metabolising enzymes (intrinsic clearance); (2) hepatic blood flow; (3) drug binding, and (4) the anatomical arrangement of the hepatic circulation. Disturbances of all these determinants can occur in chronic liver disease and result in predictable changes in propranolol disposition. These changes, as well as those occurring with other drugs in chronic liver disease, may be explained by ‘intact hepatocyte theory’ which postulates that the major pathophysiological change occuring in compensated chronic liver disease is a reduction in relatively normally perfused and functioning cell mass with the development of intrahepatic portosystemic vascular shunts.