کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9918820 1557559 2005 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis, hydrolysis, and intraocular pressure lowering effects of fadolmidine prodrugs
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
پیش نمایش صفحه اول مقاله
Synthesis, hydrolysis, and intraocular pressure lowering effects of fadolmidine prodrugs
چکیده انگلیسی
The objective of this study was to synthesize and evaluate various esters of fadolmidine, a novel alpha2-adrenergic agonist, as potential ophthalmic prodrugs. All studied prodrugs released the parent drug (i.e., fadolmidine) quantitatively via enzymatic hydrolysis in 80% human serum. The pivalyl ester was considered to be the most promising prodrug in this series, due to its good chemical stability (pH 5.0; 37 °C; t1/2 = 310 days) and optimal lipophilicity (log Papp = 1.8; 1-octanol/phosphate buffer, pH 5.0), and was selected for further evaluation of its intraocular pressure (IOP) lowering effects in normotensive rabbits. The pivalyl ester showed increased IOP lowering ability when compared to an equimolar dose of fadolmidine, which was probably due to its increased lipophilicity and subsequent enhanced corneal penetration. The duration of action for the pivalyl ester was also longer than that of fadolmidine.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 295, Issues 1–2, 13 May 2005, Pages 121-127
نویسندگان
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