[Studies on the pharmacokinetics and effects of beta-adrenergic blocking agents, sotalol (author's transl)].
Present investigation was undertaken to elucidate what pharmacokinetic parameters in animal experiment could be of more predictable for human clinical trial of beta-blocking agents. Sotalol was administered as a model drug to dogs, rats, and men. Dog experiments disclosed that the apparent volume of distribution of sotalol was about 4 times larger than the space of total body water and the plasma level of sotalol was 1.0-2.0 and 2.3-3.4 microgram/ml when the beta-blocking index showed 50 and 100% to the intravenous bolus injection of isoproterenol (0.1-1.0 microgram/kg). The clearance studies of dogs and men suggested that the elimination of sotalol depended essentially on renal excretion. The regression coefficient of beta-blocking index and plasma level of this agent in dog experiment using 0.1 microgram/kg isoproterenol was nearly equal to that of human study in which maximal exercise test was performed. Rat experiments showed a large apparent volume of distribution as well as in human study and high concentrations of sotalol in various tissues of rats. The plasma level of sotalol was well correlated with the content of the drug in such organs as heart, lung, liver, and kidneys.
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D004285:Dogs; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D005082:Physical Exertion; D051381:Rats; D013015:Sotalol / Q000008:administration & dosage / Q000378:metabolism*; D013045:Species Specificity; D014018:Tissue Distribution
D013015:Sotalol