کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486423 | 1114383 | 2011 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
QSAR Analysis of Blood-Brain Distribution: The Influence of Plasma and Brain Tissue Binding
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
Tissue binding - اتصال بافتPlasma protein binding - اتصال پروتئین پلاسماPassive diffusion - انتشار منفعلQSAR - بزرگسال Drug transport - حمل مواد مخدرIn silico modeling - در مدل سازی سیلیکاCNS - دستگاه عصبی مرکزیNonlinear Regression - رگرسیون غیرخطیBlood–brain barrier - سد خونی مغزیcomputational ADME - محاسباتی ADME
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: QSAR Analysis of Blood-Brain Distribution: The Influence of Plasma and Brain Tissue Binding QSAR Analysis of Blood-Brain Distribution: The Influence of Plasma and Brain Tissue Binding](/preview/png/2486423.png)
چکیده انگلیسی
The extent of brain delivery expressed as steady-state brain/blood distribution ratio (log BB) is the most frequently used parameter for characterizing central nervous system exposure of drugs and drug candidates. The aim of the current study was to propose a physicochemical QSAR model for log BB prediction. Model development involved the following steps: (i) A data set consisting of 470 experimental log BB values determined in rodents was compiled and verified to ensure that selected data represented drug disposition governed by passive diffusion across blood-brain barrier. (ii) Available log BB values were corrected for unbound fraction in plasma to separate the influence of drug binding to brain and plasma constituents. (iii) The resulting ratios of total brain to unbound plasma concentrations reflecting brain tissue binding were described by a nonlinear ionization-specific model in terms of octanol/water log P and pKa. The results of internal and external validation demonstrated good predictive power of the obtained model as both log BB and brain tissue binding strength were predicted with residual mean square error of 0.4 log units. The statistical parameters were similar among training and validation sets, indicating that the model is not likely to be overfitted. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2147-2160, 2011
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 6, June 2011, Pages 2147-2160
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 6, June 2011, Pages 2147-2160
نویسندگان
Kiril Lanevskij, Justas Dapkunas, Liutauras Juska, Pranas Japertas, Remigijus Didziapetris,