Dynamics of target-mediated drug disposition: how a drug reaches its target

We study the dynamics of drug–target interaction and the way it impacts the shape of drug versus time graphs through the derivation of accurate closed-form approximations, which reveal explicitly the relevance of rate constants in the system and can be used to compute such critical quantities as the...

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Bibliographic Details
Published in:Computational geosciences 2013-06, Vol.17 (3), p.599-608
Main Authors: Peletier, L. A., Gabrielsson, J.
Format: Article
Language:English
Subjects:
Computer Science
Datavetenskap (datalogi)
Drug delivery systems
Earth and Environmental Science
Earth Sciences
Geosciences, Multidisciplinary
Geotechnical Engineering & Applied Earth Sciences
Hydrogeology
Kinetics
Mathematical Modeling and Industrial Mathematics
Multidisciplinär geovetenskap
Original Paper
Pharmacology
Porous media
Soil Science & Conservation
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Summary:We study the dynamics of drug–target interaction and the way it impacts the shape of drug versus time graphs through the derivation of accurate closed-form approximations, which reveal explicitly the relevance of rate constants in the system and can be used to compute such critical quantities as the area under the ligand (drug) curve , the clearance and the terminal slope λ z . We also use these approximations to verify the validity of well-known approximate models, in particular the rapid binding model (Mager and Krzyzanski, Pharm Res 22:1589–1596, 2005 ) and the quasi-steady state model (Gibiansky et al., J Pharmacokinet Pharmacodyn 35:573–591, 2008 ).
ISSN:1420-0597
1573-1499
DOI:10.1007/s10596-012-9312-4