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

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Abstract:

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.

Keywords: (+)-sotalol; (-)-sotalol; (±)-sotalol; QTc; interval; pharmacokinetics

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1365-2125.1996.tb00113.x

Affiliations: 1: Department of Clinical Pharmacology Pharmacology, Hamamatsu University School of Medicine, Bristol-Myers Squibb K.K., Kanagawa, Japan. 2: Department of Clinical Pharmacology Metabolism and Pharmacokinetics, Biopharmaceutics Lab, Kanagawa Laboratories, Bristol-Myers Squibb K.K., Kanagawa, Japan.

Publication date: November 1, 1996

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