کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485270 | 1114351 | 2011 | 31 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
PHRMA CPCDC initiative on predictive models of human pharmacokinetics, part 5: Prediction of plasma concentration-time profiles in human by using the physiologicallyâbased pharmacokinetic modeling approach
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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
چکیده انگلیسی
The objective of this study is to assess the effectiveness of physiologically based pharmacokinetic (PBPK) models for simulating human plasma concentration-time profiles for the unique drug dataset of blinded data that has been assembled as part of a Pharmaceutical Research and Manufacturers of America initiative. Combinations of absorption, distribution, and clearance models were tested with a PBPK approach that has been developed from published equations. An assessment of the quality of the model predictions was made on the basis of the shape of the plasma time courses and related parameters. Up to 69% of the simulations of plasma time courses made in human demonstrated a medium to high degree of accuracy for intravenous pharmacokinetics, whereas this number decreased to 23% after oral administration based on the selected criteria. The simulations resulted in a general underestimation of drug exposure (Cmax and AUC0ât). The explanations for this underestimation are diverse. Therefore, in general it may be due to underprediction of absorption parameters and/or overprediction of distribution or oral firstâpass. The implications of compound properties are demonstrated. The PBPK approach based on in vitroâinput data was as accurate as the approach based on in vivo data. Overall, the scientific benefit of this modeling study was to obtain more extensive characterization of predictions of human PK from PBPK methods. © 2011 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 100:4127-4157, 2011
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 10, October 2011, Pages 4127-4157
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 10, October 2011, Pages 4127-4157
نویسندگان
Patrick Poulin, Rhys D.O. Jones, Hannah M. Jones, Christopher R. Gibson, Malcolm Rowland, Jenny Y. Chien, Barbara J. Ring, Kimberly K. Adkison, M. Sherry Ku, Handan He, Ragini Vuppugalla, Punit Marathe, Volker Fischer, Sandeep Dutta, Vikash K. Sinha,