Abstract
The pharmacokinetics of sotalol enantiomers in rats, after a single (10, 100, 300 mg/kg) and repeated (30 mg/kg/day, once daily for 7 days) oral administration of sotalol hydrochloride, were studied using stereo-selective HPLC method. Two different blood-collecting schemes were compared.
1. After a single oral administration, d- and l-sotalol showed linear pharmacokinetics in rats.
2. In the repeated administration study, the pharmacokinetics of d- and l-sotalol after first and seventh administration were not different from each other, and no accumulation was observed.
3. No enantiomeric difference was observed in the pharmacokinetics after a single and repeated administration of sotalol hydrochloride.
4. The mean urinary excretion of sotalol enantiomers within 48 hr after a single administration were about 70% for both d- and l-sotalol. The majority of the d- and l-sotalol was excreted within 24 hr.
5. Pharmacokinetics of the enantiomers were studied using two different blood-collecting protocols, (1) blood sampling from the same rats sequentially, (2) blood sampling from different rats for each time point. No significant difference on the pharmacokinetics of d- and l-sotalol was observed for both method.
6. Mean serum protein binding of d- and l-sotalol was low and accounted for approximately 9 %. No marked difference was observed between sotalol enantiomers, among species and concentrations.
