The bioavailability and kinetics of dihydroquinidine in patients with heart disease

The absolute bioavailability of dihydroquinidine chloride (normal tablet and sustained-release capsule) was studied in 12 hospitalized patients with heart disease. A 300-mg dose of dihydroquinidine gluconate was administered to each patient by short intravenous infusion. After a single dose of two tablets of dihydroquinidine chloride (300 mg), the average peak concentration was 0.74 +/- 0.43 mg/l (+/- SD); following administration two capsules of the sustained-release form (500 mg dihydroquinidine chloride) the average peak concentration was 0.55 +/- 0.25 mg/l. Tmax was approximately 5 h with the dihydroquinidine tablet and 7 h with the dihydroquinidine capsule. The mean absolute bioavailability was 89 +/- 9% for the conventional tablet and 52 +/- 15% for the sustained-release capsule. After intravenous infusion of dihydroquinidine (2.63 +/- 0.29 mg/kg), the disposition of the drug is described by a two-compartment open model. The volume of distribution (Vd) was 4.67 l/kg. Distribution (t1/2 alpha = 18.63 +/- 15.2 h) and the apparent elimination half-life (t1/2 beta = 10.8 +/- 4.7 h) were longer than the corresponding values reported by Ueda et al. [1976]. These discrepancies are presumably due to the different sampling period that was extended to 24 h in our study, consequently evidencing a slower rate of elimination from 12 to 24 h. Mean total body clearance (Cl) was 0.28 +/- 0.057 l/h/kg. Urine sample collection for 48 h showed 21% of the dose was excreted unchanged. The renal clearance (Clr) was 0.062 +/- 0.018 l/h/kg.