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Titolo:
THE AGING LIVER - DRUG CLEARANCE AND AN OXYGEN DIFFUSION BARRIER HYPOTHESIS
Autore:
LECOUTEUR DG; MCLEAN AJ;
Indirizzi:
UNIV SYDNEY,DEPT MED,YAMBA DR GARRAN ACT 2605 AUSTRALIA UNIV SYDNEY,CANBERRA HOSP,CANBERRA CLIN SCH CANBERRA ACT AUSTRALIA
Titolo Testata:
Clinical pharmacokinetics
fascicolo: 5, volume: 34, anno: 1998,
pagine: 359 - 373
SICI:
0312-5963(1998)34:5<359:TAL-DC>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFUSED-RAT-LIVER; PLASMA-PROTEIN BINDING; SPRAGUE-DAWLEY RATS; AGE-RELATED-CHANGES; SERUM-ALBUMIN; METABOLISM; PHARMACOKINETICS; DEPENDENCE; VOLUME; INJURY;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
101
Recensione:
Indirizzi per estratti:
Citazione:
D.G. Lecouteur e A.J. Mclean, "THE AGING LIVER - DRUG CLEARANCE AND AN OXYGEN DIFFUSION BARRIER HYPOTHESIS", Clinical pharmacokinetics, 34(5), 1998, pp. 359-373

Abstract

A change in drug clearance with age is considered an important factorin determining the high prevalence of adverse drug reactions associated with prescribing medications for the elderly. Despite this, no general principles have been available to guide drug administration in theelderly, although a substantial body of clearance and metabolism datahas been generated in humans and experimental animals. A review of age-related change in drug clearances established that patterns of change are not simply explained in terms of hepatic blood flow, hepatic mass and protein binding changes. In particular, the maintained clearanceof drugs subject to conjugation processes while oxygen-dependent metabolism declines, and all in vitro tests of enzyme function have been normal, requires new explanations. Reduction in hepatic oxygen diffusion as part of a general change in hepatocyte surface membrane permeability and conformation does provide one explanation for the paradoxical patterns of drug metabolism and increased hepatocyte volume would alsomodify oxygen diffusion path lengths (the 'oxygen diffusion barrier' hypothesis). The reduction in clearances of high extraction drugs doescorrelate with observed reduction in hepatic perfusion. Dosage guidelines emerge from these considerations. The dosage of high clearance drugs should be reduced by approximately 40% in the elderly while the dosage of low clearance drugs should be reduced by approximately 30%, unless the compound is principally subject to conjugation mechanisms. Ifthe hepatocyte diffusion barrier hypothesis is substantiated, this concept may lead to therapeutic (preventative and/or restorative) approaches to increased hepatocyte oxygenation in the elderly. This may leadto approaches for modification of the aging process in the liver.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 18:00:22