کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486286 | 1114379 | 2010 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Examination of the Ability of the Nasal Administration Route to Confer a Brain Exposure Advantage for Three Chemical Inhibitors of P-Glycoprotein
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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![عکس صفحه اول مقاله: Examination of the Ability of the Nasal Administration Route to Confer a Brain Exposure Advantage for Three Chemical Inhibitors of P-Glycoprotein Examination of the Ability of the Nasal Administration Route to Confer a Brain Exposure Advantage for Three Chemical Inhibitors of P-Glycoprotein](/preview/png/2486286.png)
چکیده انگلیسی
The central nervous system (CNS), efficiently isolated from the systemic circulation by the blood-brain barrier (BBB), represents a challenging therapeutic target. For CNS-targeted agents, augmenting brain exposure by increasing blood drug concentrations often is prohibited by systemic toxicity. Therefore, a means for selectively increasing brain exposure, while minimizing systemic exposure, would be desirable. Limited evidence has indicated that nasally-administered compounds can penetrate into brain, although the selectivity of this approach is unclear. This study demonstrated a distinct, but compound-specific, advantage of the nasal administration route in conferring selective CNS delivery (defined as a brain exposure advantage; BEA). Brain and systemic concentrations of three P-glycoprotein-inhibiting agents were evaluated following single nasal or systemic doses to mice, and the influence of administration route on brain exposure (absolute BEA) and on brain-to-blood partitioning (relative BEA) was calculated. Relative and absolute BEA differed markedly among rifampin, quinidine, and GF120918, with relative BEA ranging between 1.53-and 809-fold and absolute BEA between 0.114- and 9.19-fold. Although substantial increases in brain exposure and partitioning in conjunction with nasal administration were demonstrated, the utility of this approach may be limited by inability to deliver a therapeutically relevant mass of drug to the brain. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3226-3233, 2010.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 7, July 2010, Pages 3226-3233
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 7, July 2010, Pages 3226-3233
نویسندگان
Jeannie M. Padowski, Gary M. Pollack,