2009
DOI: 10.1208/s12248-009-9088-1
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Modelling and PBPK Simulation in Drug Discovery

Abstract: Abstract. Physiologically based pharmacokinetic (PBPK) models are composed of a series of differential equations and have been implemented in a number of commercial software packages. These models require species-specific and compound-specific input parameters and allow for the prediction of plasma and tissue concentration time profiles after intravenous and oral administration of compounds to animals and humans. PBPK models allow the early integration of a wide variety of preclinical data into a mechanistic q… Show more

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Cited by 170 publications
(115 citation statements)
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“…Commercially available PBPK software is used increasingly for the prediction of human PK in the pharmaceutical industry [2][3][4][5][6]. However, there are a limited number of reported studies examining the prospective performance of PBPK modeling strategies to predict clinical drug concentration profiles using the limited preclinical data available during the drug candidate selection phase.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Commercially available PBPK software is used increasingly for the prediction of human PK in the pharmaceutical industry [2][3][4][5][6]. However, there are a limited number of reported studies examining the prospective performance of PBPK modeling strategies to predict clinical drug concentration profiles using the limited preclinical data available during the drug candidate selection phase.…”
Section: Discussionmentioning
confidence: 99%
“…blood flow, organ mass) and drug properties (e.g. binding affinities, permeability) with a structural model reflecting the anatomical arrangement of the tissues connected by perfusing blood [2][3][4]. These models use physiologically relevant parameters describing absorption, distribution, metabolism and excretion (ADME) to predict the overall pharmacokinetic (PK) profile of a compound.…”
Section: Introductionmentioning
confidence: 99%
“…As described above, dilution series were prepared for each compound but with closer concentration steps (GHQ168, 5,10,15,20,25,30, and 35 g/ml; GHQ242, 150, 200, 250, 300, 350, 400, 450, and 500 g/ml; GHQ243, 50, 100, 125, 150, 175, 200, 250, and 300 g/ml; n ϭ 3 each) to end with a maximum of 2.5% residual DMSO content. Detection was accomplished nephelometrically (NEPHEOLOstar BMG, Ortenberg, Germany) using 96-well plates with a flat bottom (Greiner Bio-One, Frickenhausen, Germany).…”
Section: Methodsmentioning
confidence: 99%
“…Prior to the in vivo efficacy studies, in silico physiologically based pharmacokinetic (PBPK) modeling (20) was conducted using the Simcyp software package (Simcyp, Sheffield, United Kingdom) in order to identify a suitable dose and study design. The study design (e.g., duration, dosing interval) and the prediction of the plasma levels were performed with a mouse model.…”
Section: Methodsmentioning
confidence: 99%
“…In recent years, much progress has been achieved in PBPK modeling Thiel et al 2015;Jones et al 2009;Meyer et al 2012). Moreover, techniques of spatio-temporal tissue modeling have been established that allow simulations of how specific biological processes contribute to liver function (Hoehme et al 2017;Friebel et al 2015;Drasdo et al 2014a, b;Schliess et al 2014;Vartak et al 2016).…”
mentioning
confidence: 99%