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• W2139883819 startingPage "319" @default.
• W2139883819 abstract "Itraconazole is a fungistatic agent that, although highly lipophilic, shows poor transport through the blood brain barrier that may be due to efflux proteins. The combined administration of an efflux inhibitor with itraconazole should increase cerebral itraconazole concentrations and therefore, improve the treatment of<i>Cryptococcus neoformans</i> meningitis with this antifungal agent. To test this hypothesis, we have studied the influence of murine cerebral infection with <i>C. neoformans</i> and the inhibition of efflux by intraperitoneal injection of a P-glycoprotein inhibitor, GF120918 [<i>N</i>-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl)9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide], on the pharmacokinetics of itraconazole in plasma and brain after a single intraperitoneal itraconazole injection. We also investigated the influence of efflux inhibition on the efficacy of repeated doses of itraconazole in this murine model. The results showed that in healthy and infected mice pretreated or not with GF120918, plasma itraconazole values of area under the curve (AUC) were similar. In contrast, cerebral values of AUC were higher in infected mice compared with healthy mice. Moreover, the pretreatment of infected mice with GF120918 significantly increased cerebral itraconazole values of area under the curve and decreased weight loss in the treatment with itraconazole of a cerebral infection with <i>C. neoformans</i>." @default.
• W2139883819 created "2016-06-24" @default.
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• W2139883819 date "2003-03-01" @default.
• W2139883819 modified "2023-10-17" @default.
• W2139883819 title "Effect of Efflux Inhibition on Brain Uptake of Itraconazole in Mice Infected with<i>Cryptococcus neoformans</i>" @default.
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• W2139883819 doi "https://doi.org/10.1124/dmd.31.3.319" @default.
• W2139883819 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12584159" @default.
• W2139883819 hasPublicationYear "2003" @default.
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