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This study examines the extent of blood-brain barrier (BBB) permeation of bumetanide, a key determinant of the efficacy of centrally acting drugs. Furthermore, the impact of efflux transporter organic anion transporter 3 (oat3) inhibition on bumetanide pharmacokinetics was investigated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Bumetanide levels in extracellular fluid (ECF) and plasma in the presence and absence of oat3 inhibitor probenecid were monitored using integrated microdialysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Following a bumetanide bolus\/continuous infusion of 10 mg\/kg and 6 mg\/kg\/h, bumetanide was detected in hippocampal ECF at the estimated concentration of 131 \u00b1 55 ng\/ml. Plasma bumetanide levels were \u223c20 mg\/l at steady state. Coadministration of probenecid resulted in an increase in bumetanide levels in both ECF and plasma, indicating that oat3 inhibition influences the pharmacokinetics of bumetanide primarily in the periphery.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Although bumetanide reached detectable levels in hippocampal ECF, bumetanide concentration in ECF was low relative to systemic concentration. Oat3 inhibition by probenecid resulted in increased bumetanide concentrations in brain and plasma. As an acute treatment in neonatal seizures, the bumetanide\/probenecid combination may hold therapeutic potential.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.12341","type":"journal-article","created":{"date-parts":[[2014,12,10]],"date-time":"2014-12-10T07:15:39Z","timestamp":1418195739000},"page":"501-510","source":"Crossref","is-referenced-by-count":30,"title":["The effect of organic anion transporter 3 inhibitor probenecid on bumetanide levels in the brain: an integrated <i>in vivo<\/i> microdialysis study in the rat"],"prefix":"10.1093","volume":"67","author":[{"given":"Maria D","family":"Donovan","sequence":"first","affiliation":[{"name":"Pharmacodelivery Group, University College Cork , Cork,","place":["Ireland"]},{"name":"Department of Anatomy and Neuroscience, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fionn E","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Pharmacodelivery Group, University College Cork , Cork,","place":["Ireland"]},{"name":"Department of Anatomy and Neuroscience, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine B","family":"Boylan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Child Health, University College Cork , Cork,","place":["Ireland"]},{"name":"Irish Centre for Fetal and Neonatal Translational Research, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F","family":"Cryan","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neuroscience, University College Cork , Cork,","place":["Ireland"]},{"name":"Alimentary Pharmabiotic Centre, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan T","family":"Griffin","sequence":"additional","affiliation":[{"name":"Pharmacodelivery Group, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,4,1]]},"reference":[{"key":"2024103012491523500_jphp12341-cit-0001","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nrneurol.2009.80","article-title":"Epileptogenesis in the immature brain: emerging mechanisms","volume":"5","author":"Rakhade","year":"2009","journal-title":"Nat Rev Neurol"},{"key":"2024103012491523500_jphp12341-cit-0002","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1177\/0883073807301917","article-title":"Seizure recurrence and developmental disabilities after neonatal seizures: outcomes are unrelated to use of phenobarbital prophylaxis","volume":"22","author":"Guillet","year":"2007","journal-title":"J Child Neurol"},{"key":"2024103012491523500_jphp12341-cit-0003","volume-title":"The Epilepsies: Seizures, Syndromes and Management. 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