Verapamil disposition kinetics in chronic atrial fibrillation

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Abstract
Verapamil disposition was studied in 12 patients with chronic atrial fibrillation. After an i.v. bolus of 15 mg, plasma concentration was determined and the data fit to a 3 compartment model. Model independent parameters were calculated and values for half-life (t1/2), clearance and steady-state distribution volume were 6.3 .+-. 4 h, 13.3 .+-. 7.7 ml/min per kg and 4.3 .+-. 1.9 l/kg, respectively. The model was used to design a multistep infusion scheme, which was employed successfully to acheive predetermined plasma concentrations. Following single oral doses of 120 mg, plasma levels of verapamil and norverapamil were determined. The elimination t1/2 for verapamil and norverapamil were 8.2 .+-. 6.1 and 10.5 .+-. 5.6 h, 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. Verapamil may have reduced clearance during long-term oral use.

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