Articles
Marked Heterogeneity in the Intrahepatic Distribution of Quinidine in Rats: Implications in Pharmacokinetics

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Abstract

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 ~52-fold) or between lobes (up to ~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.

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