Analysis Methods and Recent Advances in Nonlinear Pharmacokinetics from In Vitro through In Loci to In Vivo

An attempt has been made to review the nonlinearities in the disposition in vitro, in situ, in loci and in vivo mainly from a theoretical point of view. Parallel Michaelis-Menten and linear (first-order) eliminations are often observed in the cellular uptake, metabolism and efflux of drugs. The well...

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Bibliographic Details
Published in:DRUG METABOLISM AND PHARMACOKINETICS 2004, Vol.19 (6), p.397-406
Main Authors: Yamaoka, Kiyoshi, Takakura, Yoshinobu
Format: Article
Language:English
Subjects:
Algorithms
Area Under Curve
Cells, Cultured
in loci
in situ
in vitro
in vivo
Intestinal Absorption
Michaelis-Menten
nonlinear
Nonlinear Dynamics
PBPK
Pharmacokinetics
Tissue Distribution
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Summary:An attempt has been made to review the nonlinearities in the disposition in vitro, in situ, in loci and in vivo mainly from a theoretical point of view. Parallel Michaelis-Menten and linear (first-order) eliminations are often observed in the cellular uptake, metabolism and efflux of drugs. The well-stirred and parallel-tube models are mainly adopted under steady-state conditions in perfusion experiments, whereas distribution, tank-in-series and dispersion models are often used under nonsteady-state conditions with a pulse input. The analysis of the nonlinear local disposition in loci is reviewed from two points of view, namely an indirect method involving physiologically based pharmacokinetics (PBPK) and a direct (two or three samplings) method using live animals. The nonlinear global pharmacokinetics in vivo is reviewed with regard to absorption, elimination (metabolism and excretion) and distribution.
ISSN:1347-4367
1880-0920
DOI:10.2133/dmpk.19.397