Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/12833
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dc.contributor.authorAngus, Peter Wen
dc.contributor.authorMihaly, G Wen
dc.contributor.authorMorgan, Denis Jen
dc.contributor.authorSmallwood, R Aen
dc.date.accessioned2015-05-16T02:34:44Z
dc.date.available2015-05-16T02:34:44Z
dc.date.issued1989-09-01en
dc.identifier.citationThe Journal of Pharmacology and Experimental Therapeutics; 250(3): 1043-7en
dc.identifier.govdoc2778708en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/12833en
dc.description.abstractSevere acute hypoxia is known to inhibit markedly the elimination of oxidatively metabolized drugs by the isolated liver. However, little is known of the degree of hypoxia required to produce inhibition of drug elimination by oxidative pathways in the intact organ. This study, in the isolated perfused rat liver, examined the oxygen dependence of the hepatic elimination of omeprazole, a drug which undergoes extensive oxidative metabolism in the rat. The relationship between hepatic oxygen supply and the production of omeprazole's oxidative sulfone and reductive sulfide metabolites was also examined. Rat livers were perfused at 15 ml/min with a perfusate containing 5 micrograms/ml of omeprazole in a single-pass design. Omeprazole clearance and the formation clearance of the two metabolites were measured in each liver during normal oxygenation, at different levels of hypoxia and after reoxygenation. There was a linear relationship between omeprazole clearance and oxygen delivery over the whole range studied. Production of the sulfone was similarly oxygen-dependent whereas the sulfide was only detectable after a significant reduction in oxygenation. In a further group of experiments the oxygen dependence of omeprazole clearance was shown to not be altered when the concentration of drug was lowered to 1 microgram/ml. This study shows that oxygen delivery is a critical determinant of the rate of oxidative drug metabolism in the isolated liver and supports the contention that reductions in hepatic oxygen supply may significantly alter the hepatic disposition of oxidatively metabolized drugs in vivo.en
dc.language.isoenen
dc.subject.otherAnimalsen
dc.subject.otherBile.metabolismen
dc.subject.otherDose-Response Relationship, Drugen
dc.subject.otherIn Vitro Techniquesen
dc.subject.otherLiver.metabolismen
dc.subject.otherMetabolic Clearance Rateen
dc.subject.otherOmeprazole.metabolismen
dc.subject.otherOxidation-Reductionen
dc.subject.otherOxygen.metabolismen
dc.subject.otherOxygen Consumptionen
dc.subject.otherRatsen
dc.subject.otherSulfides.metabolismen
dc.subject.otherSulfones.metabolismen
dc.titleOxygen dependence of omeprazole clearance and sulfone and sulfide metabolite formation in the isolated perfused rat liver.en
dc.typeJournal Articleen
dc.identifier.journaltitleThe Journal of pharmacology and experimental therapeuticsen
dc.identifier.affiliationGastroenterology Unit, University of Melbourne Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australiaen
dc.description.pages1043-7en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/2778708en
dc.type.austinJournal Articleen
item.grantfulltextnone-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.openairetypeJournal Article-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.languageiso639-1en-
crisitem.author.deptVictorian Liver Transplant Unit-
crisitem.author.deptGastroenterology and Hepatology-
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