{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:56:54Z","timestamp":1791316614329,"version":"4.3.1"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2014,8,1]],"date-time":"2014-08-01T00:00:00Z","timestamp":1406851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Amphotericin B (AMB) has been a mainstay therapy for fungal infections of the central nervous system, but its use has been limited by its poor penetration into the brain, the mechanism of which remains unclear. In this study, we aimed to investigate the role of P-glycoprotein (P-gp) in AMB crossing the blood-brain barrier (BBB). The uptake of AMB by primary brain capillary endothelial cells\n            <jats:italic>in vitro<\/jats:italic>\n            was significantly enhanced after inhibition of P-gp by verapamil. The impact of two model P-gp inhibitors, verapamil and itraconazole, on brain\/plasma ratios of AMB was examined in both uninfected CD-1 mice and those intracerebrally infected with\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptococcus neoformans<\/jats:named-content>\n            . In uninfected mice, the brain\/plasma ratios of AMB were increased 15 min (3.5 versus 2.0;\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) and 30 min (5.2 versus 2.8;\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) after administration of verapamil or 45 min (6.0 versus 3.9;\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) and 60 min (5.4 versus 3.8;\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) after itraconazole administration. The increases in brain\/plasma ratios were also observed in infected mice treated with AMB and P-gp inhibitors. The brain tissue fungal CFU in infected mice were significantly lower in AMB-plus-itraconazole or verapamil groups than in the untreated group (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.005), but none of the treatments protected the mice from succumbing to the infection. In conclusion, we demonstrated that P-gp inhibitors can enhance the uptake of AMB through the BBB, suggesting that AMB is a P-gp substrate.\n          <\/jats:p>","DOI":"10.1128\/aac.02535-14","type":"journal-article","created":{"date-parts":[[2014,5,28]],"date-time":"2014-05-28T07:08:08Z","timestamp":1401260888000},"page":"4464-4469","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["<i>In Vitro<\/i>\n            and\n            <i>In Vivo<\/i>\n            Evidence for Amphotericin B as a P-Glycoprotein Substrate on the Blood-Brain Barrier"],"prefix":"10.1128","volume":"58","author":[{"given":"Ji-Qin","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui-Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hui","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Qiu","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 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