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  • Title: Dose-dependent kinetics of quinidine in the perfused rat liver preparation. Kinetics of formation of active metabolites.
    Author: Yu VC, de Lamirande E, Horning MG, Pang KS.
    Journal: Drug Metab Dispos; 1982; 10(6):568-72. PubMed ID: 6130901.
    Abstract:
    The disposition of quinidine and the kinetics of metabolite formation were studied in the once-through perfused rat liver preparation by the stepwise increase in quinidine concentration. Dose-dependent kinetics of quinidine were observed; the steady-state hepatic extraction ratio decreased from 0.97 to 0.37 when input quinidine concentration varied from 1.34 to 33.9 micrograms/ml. Moreover, the formation of 3-hydroxyquinidine (detected only in perfusate as unconjugated 3-hydroxyquinidine) remained relatively linear while the formation of O-desmethylquinidine (present in bile and perfusate mostly as conjugates) apparently approached saturation kinetics within the quinidine concentrations used. The dose-dependent character of quinidine elimination cannot be attributed to changes in drug binding, as the blood/plasma ratio (4.07) and the degree of drug unbound in plasma (66.5%) remained unaltered for the quinidine concentrations used.
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