PT  - JOURNAL ARTICLE
AU  - Yu, V C
AU  - de Lamirande, E
AU  - Horning, M G
AU  - Pang, K S
TI  - Dose-dependent kinetics of quinidine in the perfused rat liver preparation. Kinetics of formation of active metabolites.
DP  - 1982 Nov 01
TA  - Drug Metabolism and Disposition
PG  - 568--572
VI  - 10
IP  - 6
4099  - http://dmd.aspetjournals.org/content/10/6/568.short
4100  - http://dmd.aspetjournals.org/content/10/6/568.full
SO  - Drug Metab Dispos1982 Nov 01; 10
AB  - 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.