Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/12822
Full metadata record
DC FieldValueLanguage
dc.contributor.authorAngus, Peter W-
dc.contributor.authorMihaly, G W-
dc.contributor.authorMorgan, Denis J-
dc.contributor.authorSmallwood, R A-
dc.date.accessioned2015-05-16T02:34:01Z
dc.date.available2015-05-16T02:34:01Z
dc.date.issued1989-05-01-
dc.identifier.citationBiochemical Pharmacology; 38(9): 1443-9en_US
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/12822en
dc.description.abstractAlthough impairment of drug metabolism by severe hypoxia is well documented in perfused liver preparations, the degree of hypoxia required to produce inhibition of drug elimination pathways in the intact liver has not been defined. In this study, in the isolated perfused rat liver, we examined the relationship between the rate of hepatic oxygen supply and the elimination rate of the drug salbutamol, which in the rat liver is eliminated largely by glucuronidation. Livers (N = 15) from male Sprague-Dawley rats were perfused in a non-recycling design with 10% human red cells in a Krebs-Henseleit electrolyte solution. Salbutamol elimination was examined during normal oxygenation (perfusate equilibrated with 100% O2; mean O2 delivery 3.21 mumol/min/g liver), at a given lower rate of oxygen delivery (achieved by producing different mixtures of N2 with O2 in the perfusate oxygenator) and after reoxygenation. In these experiments, hepatic clearance of salbutamol (perfusate concentration 50 ng/ml) was essentially independent of oxygen delivery above a rate of 2.0 mumol/min/g liver; below this level, clearance fell linearly as O2 supply was reduced. In all livers, reoxygenation restored drug elimination to control levels. In further experiments using a recycling design (N = 22), the effect of hypoxia on salbutamol elimination was found to be very similar. In recycling normoxic experiments (N = 3), the glucuronide metabolite was detected in perfusate and bile, but no sulphate metabolite was detected. While previous studies indicate that elimination of some oxidatively metabolised substrates is very sensitive to reductions in hepatic oxygenation, the present study shows that, in the isolated liver, large reductions in hepatic oxygen supply were required to produce significant impairment of the glucuronidation-dependent elimination of salbutamol.en_US
dc.language.isoenen
dc.subject.otherAlbuterol.pharmacokineticsen
dc.subject.otherAnimalsen
dc.subject.otherGlucuronates.metabolismen
dc.subject.otherHalf-Lifeen
dc.subject.otherIn Vitro Techniquesen
dc.subject.otherLiver.metabolismen
dc.subject.otherMaleen
dc.subject.otherMetabolic Clearance Rateen
dc.subject.otherOxygen.pharmacologyen
dc.subject.otherOxygen Consumptionen
dc.subject.otherPerfusionen
dc.subject.otherRatsen
dc.subject.otherRats, Inbred Strainsen
dc.titleOxygen dependence of salbutamol elimination by the isolated perfused rat liver.en_US
dc.typeJournal Articleen_US
dc.identifier.journaltitleBiochemical Pharmacologyen_US
dc.identifier.affiliationMedicine (University of Melbourne)en_US
dc.description.pages1443-9en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/2719719en
dc.type.contentTexten_US
dc.type.austinJournal Articleen
local.name.researcherAngus, Peter W
item.languageiso639-1en-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.cerifentitytypePublications-
item.openairetypeJournal Article-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
crisitem.author.deptVictorian Liver Transplant Unit-
crisitem.author.deptGastroenterology and Hepatology-
Appears in Collections:Journal articles
Show simple item record

Page view(s)

8
checked on Mar 3, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.