{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:45:26Z","timestamp":1791405926480,"version":"4.3.3"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2981,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2000,12]]},"abstract":"<jats:p><jats:list list-type=\"explicit-label\"><jats:list-item><jats:p>The objective of this study was to investigate the impact of probenecid on the blood\u2010brain barrier (BBB) transport of morphine\u20103\u2010glucuronide (M3G).<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Two groups of rats received an exponential infusion of M3G over 4\u2003h to reach a target plasma concentration of 65\u2003\u03bc<jats:sc>M<\/jats:sc>on two consecutive days. Probenecid was co\u2010administered in the treatment group on day 2. Microdialysis was used to estimate unbound M3G concentrations in brain extracellular fluid (ECF) and blood.<jats:italic>In vivo<\/jats:italic>recovery of M3G was calculated with retrodialysis by drug, preceding the drug administration. The BBB transport was modelled using NONMEM.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In the probenecid group, the ratio of the steady\u2010state concentration of unbound M3G in brain ECF to that in blood was 0.08\u00b10.02 in the absence and 0.16\u00b10.05 in the presence of probenecid (<jats:italic>P<\/jats:italic>=0.001). In the control group, no significant difference was found in this ratio between the 2 days (0.11\u00b10.05 and 0.10\u00b10.02, respectively). The process that appears to be mainly influenced by probenecid is influx clearance into the brain (0.11\u2003\u03bcl\u2003min<jats:sup>\u22121<\/jats:sup>\u2003g\u2010brain<jats:sup>\u22121<\/jats:sup><jats:italic>vs<\/jats:italic>0.17\u2003\u03bcl\u2003min<jats:sup>\u22121<\/jats:sup>\u2003g\u2010brain<jats:sup>\u22121<\/jats:sup>, in the absence<jats:italic>vs<\/jats:italic>presence of probenecid,<jats:italic>P<\/jats:italic>&lt;0.001). The efflux clearance was 1.15\u2003\u03bcl\u2003min<jats:sup>\u22121<\/jats:sup>\u2003g\u2010brain<jats:sup>\u22121<\/jats:sup>. The half\u2010life of M3G was 81\u00b125\u2003min in brain ECF<jats:italic>vs<\/jats:italic>22\u00b12\u2003min in blood (<jats:italic>P<\/jats:italic>&lt;0.0001). Blood pharmacokinetics was not influenced by probenecid.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In conclusion, a probenecid\u2010sensitive transport system is involved in the transport of M3G across the BBB.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic>(2000)<jats:bold>131<\/jats:bold>, 1784\u20131792; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703759\">10.1038\/sj.bjp.0703759<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703759","type":"journal-article","created":{"date-parts":[[2010,12,17]],"date-time":"2010-12-17T14:57:00Z","timestamp":1292597820000},"page":"1784-1792","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Modelling of the blood\u2010brain barrier transport of morphine\u20103\u2010glucuronide studied using microdialysis in the rat: involvement of probenecid\u2010sensitive transport"],"prefix":"10.1111","volume":"131","author":[{"given":"Rujia","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Ren\u00e9","family":"Bouw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margareta","family":"Hammarlund\u2010Udenaes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/S0022-3565(25)39013-0","article-title":"Contribution of probenecid\u2010sensitive anion transport processes at the brain capillary endothelium and choroid plexus to the efficient efflux of valproic acid from the central nervous system","volume":"268","author":"ADKISON K.D.K.","year":"1994","journal-title":"J. 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