کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485274 | 1114351 | 2011 | 24 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
PhRMA CPCDC Initiative on Predictive Models of Human Pharmacokinetics, Part 1: Goals, Properties of the Phrma Dataset, and Comparison with Literature Datasets
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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
![عکس صفحه اول مقاله: PhRMA CPCDC Initiative on Predictive Models of Human Pharmacokinetics, Part 1: Goals, Properties of the Phrma Dataset, and Comparison with Literature Datasets PhRMA CPCDC Initiative on Predictive Models of Human Pharmacokinetics, Part 1: Goals, Properties of the Phrma Dataset, and Comparison with Literature Datasets](/preview/png/2485274.png)
چکیده انگلیسی
This study is part of the Pharmaceutical Research and Manufacturers of America (PhRMA) initiative on predictive models of efficacy, safety, and compound properties. The overall goal of this part was to assess the predictability of human pharmacokinetics (PK) from preclinical data and to provide comparisons of available prediction methods from the literature, as appropriate, using a representative blinded dataset of drug candidates. The key objectives were to (i) appropriately assemble and blind a diverse dataset of in vitro, preclinical in vivo, and clinical data for multiple drug candidates, (ii) evaluate the dataset with empirical and physiological methodologies from the literature used to predict human PK properties and plasma concentration-time profiles, (iii) compare the predicted properties with the observed clinical data to assess the prediction accuracy using routine statistical techniques and to evaluate prediction method(s) based on the degree of accuracy of each prediction method, and (iv) compile and summarize results for publication. Another objective was to provide a mechanistic understanding as to why one methodology provided better predictions than another, after analyzing the poor predictions. A total of 108 clinical lead compounds were collected from 12 PhRMA member companies. This dataset contains intravenous (n = 19) and oral pharmacokinetic data (n = 107) in humans as well as the corresponding preclinical in vitro, in vivo, and physicochemical data. All data were blinded to protect the anonymity of both the data and the company submitting the data. This manuscript, which is the first of a series of manuscripts, summarizes the PhRMA initiative and the 108 compound dataset. More details on the predictability of each method are reported in companion manuscripts. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4050-4073, 2011
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 10, October 2011, Pages 4050-4073
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 10, October 2011, Pages 4050-4073
نویسندگان
Patrick Poulin, Hannah M. Jones, Rhys Do Jones, James W.T. Yates, Christopher R. Gibson, Jenny Y. Chien, Barbara J. Ring, Kimberly K. Adkison, Handan He, Ragini Vuppugalla, Punit Marathe, Volker Fischer, Sandeep Dutta, Vikash K. Sinha, Thorir Björnsson,