کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486050 | 1114373 | 2010 | 19 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A Physiologically Based Pharmacokinetic (PBPK) Model for Predicting the Efficacy of Drug Overdose Treatment With Liposomes in Man
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کلمات کلیدی
Toxicokinetics - تاکسیکوسینتیک، تاکسیکوکینتیکDrug transport - حمل مواد مخدرDynamic simulation - شبیه سازی پویاSimulations - شبیهسازی یا سیمولاسیونPharmacokinetics - فارماکوکینتیکLiposomes - لیپوزومPhysiological model - مدل فیزیولوژیکیpharmacokinetic/pharmacodynamic models - مدل های فارماکوکینتیک / فارماکودینامیکTissue partition - پارتیشن بافت
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Physiologically based pharmacokinetic (PBPK) models were developed for design and optimization of liposome therapy for treatment of overdoses of tricyclic antidepressants and local anesthetics. In vitro drug-binding data for pegylated, anionic liposomes and published mechanistic equations for partition coefficients were used to develop the models. The models were proven reliable through comparisons to intravenous data. The liposomes were predicted to be highly effective at treating amitriptyline overdoses, with reductions in the area under the concentration versus time curves (AUC) of 64% for the heart and brain. Peak heart and brain drug concentrations were predicted to drop by 20%. Bupivacaine AUC and peak concentration reductions were lower at 15.4% and 17.3%, respectively, for the heart and brain. The predicted pharmacokinetic profiles following liposome administration agreed well with data from clinical studies where protein fragments were administered to patients for overdose treatment. Published data on local cardiac function were used to relate the predicted concentrations in the body to local pharmacodynamic effects in the heart. While the results offer encouragement for future liposome therapies geared toward overdose, it is imperative to point out that animal experiments and phase I clinical trials are the next steps to ensuring the efficacy of the treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 8, August 2010, Pages 3601-3619
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 8, August 2010, Pages 3601-3619
نویسندگان
Brett A. Howell, Anuj Chauhan,