Prediction of serum concentration time course of quinidine in human using a physiologically based pharmacokinetic model developed from the rat.
Serum concentration-time courses of quinidine in humans were predicted by a physiologically based pharmacokinetic model developed from the rat using reported values for the serum protein binding, blood-to-serum concentration ratio, renal clearance and physiological constants, i.e. tissue volume and blood flow rate of each tissue. The tissue binding parameters of the rat were used for humans. The hepatic intrinsic clearance (CLH,int) of quinidine for human was extrapolated by using the relation between CLH,int of humans and those of the rat reported for antipyrine, phenytoin and hexobarbital. The predicted time courses were comparable with the observed data in humans obtained from the literature, though slight differences were shown in the half-lives between the observed data and the predicted curves. It was suggested that the overestimation of the tissue binding parameters might be the cause of this difference.
Harashima
H
H
Sawada
Y
Y
Sugiyama
Y
Y
Iga
T
T
Hanano
M
M
D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D006207:Half-Life; D006591:Hexobarbital / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D010672:Phenytoin / Q000378:metabolism; D011802:Quinidine / Q000097:blood*; D051381:Rats; D013997:Time Factors
D010672:Phenytoin; D006591:Hexobarbital; D011802:Quinidine; D000983:Antipyrine