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Clinical Pharmacokinetics

, Volume 1, Issue 2, pp 135–155 | Cite as

Altered Hepatic Blood Flow and Drug Disposition

  • Alan S. Nies
  • David G. Shand
  • Grant R. Wilkinson
Article

Summary

For some drugs, delivery to the liver by the hepatic circulation is an important determinant of removal by this organ. Classical pharmacokinetic analyses cannot predict the changes produced by altering any of the biological determinants of drug elimination by the liver; hepatic blood flow, metabolic enzyme activity, drug binding and route of administration. However, with the use of a physiological model of hepatic drug elimination, such predictions can be made. This model has been tested experimentally and appears to be valid.

Hepatic blood flow can vary over about a 4-fold range from half normal flow to twice normal flow. These variations are produced by physiological, pathological or pharmacological changes affecting the circulation. For drug clearance to be affected significantly by these changes in flow, the drug must be avidly removed by the liver as reflected in a high hepatic extraction ratio and intrinsic hepatic clearance. This latter term is a useful way to characterise the ability of the liver to irreversibly remove drug from the circulation in the absence of any flow limitation. The clearance of drugs with low intrinsic clearances will not be affected significantly by changes in liver blood flow.

Keywords

Antipyrine Lignocaine Phenobarbitone Hepatic Blood Flow Drug Clearance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© ADIS Press 1976

Authors and Affiliations

  • Alan S. Nies
    • 1
  • David G. Shand
    • 1
  • Grant R. Wilkinson
    • 1
  1. 1.Division of Clinical Pharmacology, Departments of Medicine and PharmacologyVanderbilt University School of MedicineNashvilleUSA

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