Authors: Jens Aa Jansen
Publish Date: 1981/02/01
Volume: 9, Issue: 1, Pages: 15-26
Abstract
The potential influence of protein binding kinetics on elimination from liver sinusoids was evaluated by means of a “wellstirred” model I and a “tube” model II When the dissociation rate constant k−1 is at the estimated maximum equilibrium is maintained during the passage of drug through the eliminating organ and hence dissociation as such has no limiting effect on elimination When however k−1 is at the estimated minimum equilibrium is not maintained the unbound fraction is reduced during the passage and a significant decrease in the extraction ratio occurs when the unbound fraction is 001 or less The models were furthermore used to investigate the effect of saturation of both the binding protein and the elimination process on elimination
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