Oral and IV dosing: a method to determine the compartment of drug elimination for two-compartment models.
It has been shown previously that it is impossible to measure the volume of distribution at steady state conclusively for a multicompartment system from an iv bolus dose only. The problem lies in deciding from which compartment elimination of the drug occurs in the compartmental model. In this paper a new modelling strategy is examined whereby the compartment of elimination may be identified uniquely for the case of two-compartment models. The two models examined predict different profiles in the absorption phase of an oral profile. An in vivo data set is provided that favours a peripheral elimination explanation of its observed pharmacokinetics, based on the 'goodness of fit'.
Yates
J W T
JW
Discovery DMPK, AstraZeneca, Alderley Park, Cheshire SK10 4TG, UK. James.Yates@astrazeneca.com
Arundel
P A
PA
D000284:Administration, Oral; D000818:Animals; D006801:Humans; D007275:Injections, Intravenous; D008954:Models, Biological; D010599:Pharmacokinetics; D015203:Reproducibility of Results