Evaluation of once daily sotalol administration in man.

Sotalol 400 mg orally was given to five healthy male volunteers as a single dose and then subsequently once daily for 8 days. Following the single dose and again after the eighth daily dose, blood samples were obtained at 3, 7, 12, 24, 36 and 48 h for plasma sotalol estimation. During the 8-day course of sotalol 400 mg once daily, the effect was assessed by exercise testing and blood samples drawn for plasma sotalol measurement at 0 and 3 h with each dose. The elimination half-life after chronic administration (17.7 ± 2.6 h) was not significantly different from that obtained after the single dose (15.5 ± 1.2 h). No difference occurred either in the comparable plasma concentrations on both elimination curves. It would appear, therefore, that chronic administration of sotalol does not alter its kinetics. Drug accumulation, measured as AUC / AUC, showed a mean value of 0.95 ± 0.18, indicating that accumulation had not occurred. Mean reduction of exercise heart rate ranged from a minimum of 20.5 ± 2.0% at time 0 on Day 8 to a maximum of 38.7 ± 1.1% at +3 h on Day 4. The minimum blockade in any individual during the 8 days was 14.5%. There was a significant correlation between percentage reduction in exercise heart rate and plasma sotalol concentration. Once daily administration of sotalol 400 mg orally would, therefore, appear to be an effective therapeutic regimen when sustained β-adrenoceptor blockade is required.