Pharmacokinetics and pharmacodynamics of ()‐sotalol in healthy male volunteers

1 We investigated the pharmacokinetics and pharmacodynamics of (±)‐sotalol administered orally to healthy male volunteers in single doses of 40, 80 and 160 mg and in multiple doses of 80 mg twice daily for 7 consecutive days.

2 In the single dose studies, the half‐life of (‐)‐sotalol (7.2‐8.5 h) was significantly (P < 0.01) shorter than that of (+)‐sotalol (9.1‐11.4 h) while the renal clearance of (‐)‐sotalol (110.6‐126.4 ml min^‐1) was significantly (P < 0.01) faster than that of (+)‐sotalol (102.2‐110.1 ml min^‐1). In the multiple dose studies, similar differences in the pharmacokinetics of (+)‐ and (‐)‐sotalol were observed. In addition, the pharmacokinetics of both (+)‐ and (‐)‐sotalol on day 4 were shown to be essentially the same as those on day 7.

3 In pharmacodynamic examinations, (±)‐sotalol prolonged QTc intervals on electrocardiograms dose‐dependently after single doses of 80 and 160 mg (3.81 ± 2.96%, 13.23 ± 5.66%). The correlation between the plasma concentration of (±)‐sotalol and prolongation of QTc intervals was nearly linear, and showed no hysteresis.

4 In conclusion, we demonstrated that QTc interval was prolonged with a linear correlation to the plasma concentration of (±)‐sotalol. In addition, our study suggested that differences in the pharmacokinetics of (+)‐ and (‐)‐sotalol may be attributable to faster urinary excretion of (‐)‐sotalol.

DOI: 10.1111/j.1365-2125.1996.tb00113.x

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