Altered hepatic blood flow and drug disposition
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 logical 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 clearance will not be affected significantly by changes in liver blood flow.
Medienart: |
Artikel |
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Erscheinungsjahr: |
1976 |
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Erschienen: |
1976 |
Enthalten in: |
Zur Gesamtaufnahme - volume:1 |
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Enthalten in: |
Clinical pharmacokinetics - 1(1976), 2 vom: 05., Seite 135-55 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Nies, A S [VerfasserIn] |
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Themen: |
9Y8NXQ24VQ |
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Anmerkungen: |
Date Completed 25.04.1977 Date Revised 13.11.2018 published: Print Citation Status MEDLINE |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM000147575 |
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245 | 1 | 0 | |a Altered hepatic blood flow and drug disposition |
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500 | |a Date Completed 25.04.1977 | ||
500 | |a Date Revised 13.11.2018 | ||
500 | |a published: Print | ||
500 | |a Citation Status MEDLINE | ||
520 | |a 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 logical 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 clearance will not be affected significantly by changes in liver blood flow | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Review | |
650 | 7 | |a Adrenergic alpha-Agonists |2 NLM | |
650 | 7 | |a Anesthetics |2 NLM | |
650 | 7 | |a Pharmaceutical Preparations |2 NLM | |
650 | 7 | |a Propranolol |2 NLM | |
650 | 7 | |a 9Y8NXQ24VQ |2 NLM | |
650 | 7 | |a Phenobarbital |2 NLM | |
650 | 7 | |a YQE403BP4D |2 NLM | |
700 | 1 | |a Shand, D G |e verfasserin |4 aut | |
700 | 1 | |a Wilkinson, G R |e verfasserin |4 aut | |
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