کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8994659 | 1114441 | 2005 | 18 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Physiologically Based Pharmacokinetic Modeling 1: Predicting the Tissue Distribution of Moderate-to-Strong Bases
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کلمات کلیدی
QSAR - بزرگسال Physicochemical properties - خواص فیزیکی و شیمیاییIn silico modeling - در مدل سازی سیلیکاPartition coefficients - ضرایب پارتیشنPharmacokinetics - فارماکوکینتیکPhospholipids - فسفولیپیدPBPK modeling - مدل سازی PBPKPhysiological model - مدل فیزیولوژیکیBeta-Blockers - مسدود کننده های بتاTissue partition - پارتیشن بافت
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
Tissue-to-plasma water partition coefficients (Kpu's) form an integral part of whole body physiologically based pharmacokinetic (WBPBPK) models. This research aims to improve the predictability of Kpu values for moderate-to-strong bases (pKa â¥Â 7), by developing a mechanistic equation that accommodates the unique electrostatic interactions of such drugs with tissue acidic phospholipids, where the affinity of this interaction is readily estimated from drug blood cell binding data. Additional model constituents are drug partitioning into neutral lipids and neutral phospholipids, and drug dissolution in tissue water. Major assumptions of this equation are that electrostatic interactions predominate, drugs distribute passively, and non-saturating conditions prevail. Resultant Kpu predictions for 28 moderate-to-strong bases were significantly more accurate than published equations with 89%, compared to 45%, of the predictions being within a factor of three of experimental values in rat adipose, bone, gut, heart, kidney, liver, muscle, pancreas, skin, spleen and thymus. Predictions in rat brain and lung were less accurate probably due to the involvement of additional processes not incorporated within the equation. This overall improvement in prediction should facilitate the further application of WBPBPK modeling, where time, cost and labor requirements associated with experimentally determining Kpu's have, to a large extent, deterred its application. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 94, Issue 6, June 2005, Pages 1259-1276
Journal: Journal of Pharmaceutical Sciences - Volume 94, Issue 6, June 2005, Pages 1259-1276
نویسندگان
Trudy Rodgers, David Leahy, Malcolm Rowland,