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dc.contributor.authorHughes, Jeffery
dc.contributor.authorCrowe, Andrew
dc.contributor.editorKim Brosen and Michael Mulvany
dc.date.accessioned2017-01-30T12:03:59Z
dc.date.available2017-01-30T12:03:59Z
dc.date.created2010-12-20T20:02:42Z
dc.date.issued2010
dc.identifier.citationHughes, Jeff and Crowe, Andrew. 2010. Inhibition of P-glycoprotein - Mediated Efflux of Digoxin and Its Metabolites by Macrolide Antibiotics. Journal of Pharmacological Sciences. 113 (4): pp. 315-324.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/17778
dc.identifier.doi10.1254/jphs.10109FP
dc.description.abstract

This study was conducted to determine the rate of P-glycoprotein (P-gp) mediated efflux of digoxin analogues and metabolites, and to assess the effects of macrolide antibiotics on this efflux. Bidirectional transport studies were conducted using our Caco-2 sub clone with high P-gp expression (CLEFF9). HPLC methods were employed to measure drug transport. All digoxin metabolites were P-gp substrates, although digoxin had the greatest efflux ratio. Erythromycin had no effect on the transport of digoxin, maintaining a Basolateral to apical efflux ratio of 14.8, although it did reduce the efflux ratio of dihydrodigoxin and digoxigenin by 34% and 43%, respectively. Azithromycin also had little effect on the transport of digoxin or any of its metabolites. In contrast, clarithromycin and roxithromycin almost eliminated basolateral targeted efflux. Using paclitaxel as a known P-gp substrate, erythromycin demonstrated only partial P-gp inhibitory capacity maintaining an efflux ratio over 100. In contrast, clarithromycin and roxithromycin were 10 fold greater P-gp inhibitors. Clarithromycin and roxithromycin are likely to exhibit drug interactions with digoxin via inhibition of efflux mechanisms. Azithromycin appears to have little influence on P-gp mediated digoxin absorption or excretion and would be the safest macrolide to use concurrently with oral digoxin.

dc.publisherThe Japanese Pharmacological Society
dc.subjectclarithromycin
dc.subjectCaco-2
dc.subjectP-glycoprotein
dc.subjecterythromycin
dc.subjectazithromycin
dc.titleInhibition of P-glycoprotein - Mediated Efflux of Digoxinand Its Metabolites by Macrolide Antibiotics
dc.typeJournal Article
dcterms.source.volume113
dcterms.source.startPage315
dcterms.source.endPage324
dcterms.source.issn1347-8613
dcterms.source.titleJournal of Pharmacological Sciences
curtin.departmentSchool of Pharmacy
curtin.accessStatusOpen access


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