Irreversible CYP3A Inhibition Accompanied by Plasma Protein–Binding Displacement: A Comparative Analysis in Subjects With Normal and Impaired Liver Function

Age-related changes in physiology and pharmacokinetics (how drugs are used in the body) lead to increased drug sensitivity and potentially harmful drug effects. This report addresses the heightened sensitivity to drug effects seen in older adults. The first section of the report presents three examples of physiologic decline: a) decreased plasma protein binding affects drug distribution, b) declining liver function affects drug metabolism, and c) impaired kidney function delays drug elimination. The next section illustrates by example the risks associated with altered physiology: a) decline in plasma protein binding may result in an intensified effect of the drug Phenytoin, b) altered liver function increases the sedative effects of Diazepam, and c) declining kidney function results in accumulation of the drug Gentamicin, where toxic effects include kidney failure and deafness. The last section is a discussion of some broad considerations for geriatric pharmacology. Adverse drug reactions can largely be avoided by carefully weighing the needs and clinical status of older persons on an individual basis both prior to and throughout the course of a given drug therapy.

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Urokinase Antigen in Plasma of Patients with Liver Cirrhosis and Hepatoma

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660082 ◽

1985 ◽

Vol 54 (03) ◽

pp. 617-618 ◽

Cited By ~ 15

Author(s):

J C Kirchheimer ◽

K Huber ◽

P Polterauer ◽

B R Binder

Keyword(s):

Liver Cirrhosis ◽

Liver Disease ◽

Liver Function ◽

Matched Control ◽

Malignant Growth ◽

Control Groups ◽

Impaired Liver Function ◽

Impaired Liver ◽

Specific Medication ◽

History Of

SummaryPlasma urokinase antigen levels were studied in 78 patients suffering from liver diseases. Blood was drawn before any specific medication was initiated. Impairment of liver function was comparable in all patients. In both groups of cirrhotic liver disease (alcoholic and non-alcoholic), normal levels of plasma urokinase antigen were found as compared to age-matched control groups. In both groups of patients with hepatomas (with or without a history of liver cirrhosis), however, significantly increased plasma urokinase antigen levels could be determined. These data indicate that an increase in plasma urokinase antigen might rather relate to malignant growth in liver disease than to impaired liver function.

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Faculty Opinions recommendation of Matched molecular pairs as a guide in the optimization of pharmaceutical properties; a study of aqueous solubility, plasma protein binding and oral exposure.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1046889.496914 ◽

2006 ◽

Author(s):

Michael Gelb

Keyword(s):

Protein Binding ◽

Plasma Protein Binding ◽

Plasma Protein ◽

Aqueous Solubility ◽

Oral Exposure ◽

Matched Molecular Pairs ◽

Pharmaceutical Properties

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