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Effect of Efflux Transporter Inhibition on the Distribution of Fluconazole in the Rat Brain

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Abstract

Multidrug resistance-associated proteins (MRPs) and organic anion transporters (OATs) are expressed on the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), preventing the entry of or the pumping out of numerous molecules. Fluconazole is widely used to treat fungal meningoencephalitis. The effect of these transporters on the distribution of fluconazole in the brain is unclear. We used microdialysis to compare the distribution of fluconazole in the rat brain with and without co-administration of probenecid, a MRP and OAT inhibitor. Additionally, we also observed the difference in fluconazole distribution between the two barriers. The results showed that probenecid increased the penetration of fluconazole into the BBB but did not alter the penetration of fluconazole into the BCSFB of rats. The penetration of the BBB and BCSFB by fluconazole did not statistically differ according to physiological condition. These results demonstrate that transporters that can be inhibited by probenecid may be involved in fluconazole resistance at the BBB and provide a laboratory basis for predicting brain extracellular fluid (ECF) concentration using the cerebrospinal fluid (CSF) concentration of fluconazole.

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Acknowledgements

This study was supported by the General Hospital of People’s Liberation Army grant CWS11J064. We appreciate the technical and equipment support provided by Dr. Zheng Yong from the Academy of Military Medical Sciences.

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Authors and Affiliations

  1. Department of Neurology, General Hospital of People’s Liberation Army, No. 28, Fuxing Road, Haidian District, Beijing, 100853, China

    Wei Wang, Na Zheng, Jiatang Zhang, Xusheng Huang & Shengyuan Yu

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  1. Wei Wang
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  2. Na Zheng
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  3. Jiatang Zhang
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  4. Xusheng Huang
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  5. Shengyuan Yu
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Correspondence to Jiatang Zhang.

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Wang, W., Zheng, N., Zhang, J. et al. Effect of Efflux Transporter Inhibition on the Distribution of Fluconazole in the Rat Brain. Neurochem Res 42, 2274–2281 (2017). https://doi.org/10.1007/s11064-017-2240-x

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  • DOI: https://doi.org/10.1007/s11064-017-2240-x

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