Evaluation of once daily sotalol administration in man.

1 Sotalol 400 mg orally was given to five healthy male volunteers as a single dose and then subsequently once daily for 8 days. 2 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. 3 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. 4 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. 5 Drug accumulation, measured as AUC(ss) / AUC(1), showed a mean value of 0.95 ± 0.18, indicating that accumulation had not occurred. 6 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%. 7 There was a significant correlation between percentage reduction in exercise heart rate and plasma sotalol concentration. 8 Once daily administration of sotalol 400 mg orally would, therefore, appear to be an effective therapeutic regimen when sustained β-adrenoceptor blockade is required.