Statistical moments and disposition parameters in a local perfusion system under mammillary nonequilibrium condition.
Application of the statistical moment analysis to the local organ perfusion system leads moment parameters (moments) from the venous outflow concentration-time curve (dilution curve) of drug after its intra-arterial bolus injection. By introducing the chromatographic concept and the network theory, we had defined the disposition parameters such as steady state distribution volume, mean elimination time, and intrinsic clearance from moments based on the well-stirred model. In this paper, discussion was expanded to general two-compartment organ perfusion models and the meanings of these disposition parameters in them were investigated. The relationship between compartmentally defined microconstants and moments-oriented disposition parameters was examined and the effect of the nonequilibrium (mainly peripheral elimination) condition on the latter was discussed. The possible utility of the disposition parameters as noncompartmental indications of drug disposition characteristics was suggested.
Kakutani
T
T
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Nara
E
E
Hashida
M
M
D008954:Models, Biological; D010477:Perfusion; D010599:Pharmacokinetics; D013223:Statistics as Topic / Q000379:methods*