Verapamil administration in patients with chronic atrial fibrillation showed 35% oral bioavailability, with long-term oral therapy yielding plasma concentrations twice the predicted single-dose value.
What are the disposition kinetics of verapamil following intravenous and oral administration in patients with chronic atrial fibrillation?
Verapamil exhibits reduced clearance during long-term oral therapy compared to single-dose predictions in patients with chronic atrial fibrillation.
Verapamil disposition was studied in 12 patients with chronic and fibrillation. After an intravenous bolus of 15 mg plasma concentration was determined and the data fit in a three-compartment model. Model independent parameters were calculated and values for half-life (t 1/2), clearance, and steady-state distribution volume were 6.3 +/- 4 hr, 13.3 +/- 7.7 ml/min/kg, and 4.3 +/- 1.9 l/kg. The model was used to design a multistep infusion scheme, which was employed successfully to achieve predetermined plasma concentrations. Following single oral doses of 120 mg, plasma levels of verapamil and norverapamil were determined. The elimination t 1/2 for verapamil and norverapamil were 8.3 +/- 6.1 and 10.5 +/- 5.6 hr, respectively. The bioavailability of oral verapamil was 35 +/- 16%. During long-term oral therapy the mean verapamil plasma concentration was twice the value predicted from the single-dose studies. This suggests that verapamil may have reduced clearance during long-term oral use.
Kates et al. (1981) studied chronic atrial fibrillation (n=12). Verapamil was evaluated on Verapamil disposition kinetics (half-life, clearance, steady-state distribution volume, and bioavailability). Verapamil administration in patients with chronic atrial fibrillation showed 35% oral bioavailability, with long-term oral therapy yielding plasma concentrations twice the predicted single-dose value.