Dose-dependence of the pharmacokinetics of quinidine

Quinidine was administrated orally to five healthy male volunteers. Doses of 0.2 g t.i.d., 0.3 g t.i.d. and 0.4 g t.i.d. were given for five days with at least four weeks between each test period. The plasma concentration of quinidine was measured before the morning dose on Days 2-5 of treatment, and 1, 2, 4 and 8 h after the morning dose on the 5th day. There was not a linear relationship between the increase in dose and the increase in plasma concentration of quinidine. A dose increase of 50% from 0.6 to 0.9 g quinidine sulphate per day resulted in an increase in steady state concentration of 94%. A further 33% increase in dose, from 0.9 to 1.2 g daily, resulted in a 55% increase in the steady state concentration of quinidine. The results demonstrate dose-dependent pharmacokinetics for quinidine. Possible explanations for the nonlinear pharmacokinetics are discussed.