Marked heterogeneity in the intrahepatic distribution of quinidine in rats: implications in pharmacokinetics.
Approximately 20 to 24 samples (0.1-0.2 g each) were obtained from each of six isolated rat livers following steady-state infusion of quinidine. The concentrations of quinidine, analyzed by an HPLC method, were found to vary markedly within each lobe (up to approximately 52-fold) or between lobes (up to approximately 25-fold) from the same liver. The maximum intrahepatic concentration difference in the six livers studied was 208-fold. Implications of the present study in the determination of liver drug concentration, and of the partition coefficient between liver and venous drug concentration in physiological pharmacokinetic modeling, as well as in hepatic modeling, are discussed.
Lee
H J
HJ
Department of Pharmacodynamics, College of Pharmacy, University of Illinois, Chicago 60612.
Chiou
W L
WL
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D011802:Quinidine / Q000493:pharmacokinetics*; D051381:Rats
D011802:Quinidine