کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487658 | 1114426 | 2007 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Assessing the antifungal activity, pharmacokinetics, and tissue distribution of amphotericin B following the administration of Abelcet® and AmBisome® in combination with caspofungin to rats infected with Aspergillus fumigatus
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The purpose of this study was to assess the antifungal activity, pharmacokinetics, and tissue distribution of amphotericin B (AmpB) following the administration of Abelcet® and AmBisome® alone and in combination with Caspofungin® to rats infected with Aspergillus fumigatus. Aspergillus fumigatus inoculum (2.1â2.5 Ã 107 colony forming units [CFU]) was injected via the jugular vein; 48Â h later male albino Sprague-Dawley rats (350-400 g) were administered either a single intravenous (i.v.) dose of Abelcet® (5Â mg AmpB/kg; n = 6), AmBisome® (5Â mg AmpB/kg; n = 6), Caspofungin® (3Â mg/kg; n = 5), Abelcet® (5Â mg AmpB/kg) plus Caspofungin® (3Â mg/kg) (n = 6), AmBisome® (5Â mg AmpB/kg) plus Caspofungin® (3Â mg/kg) (n = 7), or physiologic saline (nonâtreated controls; n = 6) once daily for 4 days. Antifungal activity was assessed by organ CFU concentrations and plasma galactomannan levels. Plasma and tissue samples were taken from each animal for AmpB pharmacokinetic analysis and tissue distribution determinations. Abelcet® treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 73% compared to nonâtreated controls. Ambisome® treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 69% compared to nonâtreated controls. Caspofungin® treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 80% compared to nonâtreated controls. Abelcet® plus Caspofungin® treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 81% compared to nonâtreated controls. Ambisome® plus Caspofungin® treatment significantly decreased total fungal CFU concentrations recovered in all the organs added together by 98% compared to nonâtreated controls. Abelcet® treatment significantly decreased plasma galactomannan levels by 50 and 75% 96Â h following the initiation of treatment in the absence and presence of Caspofungin coâtherapy, respectively. AmBisome® treatment significantly decreased plasma galactomannan levels by 73 and 78% 96Â h following the initiation of treatment in the absence and presence of Caspofungin coâtherapy, respectively. Coâadministration of Caspofungin with Abelcet and AmBisome did not significantly alter the plasma concentrationâtime profile, pharmacokinetic parameters, and tissue distribution of AmpB. Taken together, our findings suggest that an alternative mechanism, possibly at the cellular level rather than altered AmpB disposition, may be an explanation for the differences in organ CFU concentrations following Abelcet® plus Caspofungin versus AmBisome® plus Caspofungin administration. © 2006 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1737-1747, 2007
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 7, July 2007, Pages 1737-1747
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 7, July 2007, Pages 1737-1747
نویسندگان
Kishor M. Wasan, Olena Sivak, Michael Rosland, Verica Risovic, Karen Bartlett,