Bidisomide (SC‐40230), a new antiarrhythmic agent: Initial study of tolerability and pharmacokinetics

Forty‐nine healthy male volunteers received the test article for bidisomide (SC‐40230) in a double‐blind, placebo‐controlled, dose‐ranging study. Intravenous doses ranged from 0.03 to 2.5 mg/kg. There was a close relationship between the dose and the peak plasma concentration. The PR, QRS, QT, RR, and QTc intervals each demonstrated a statistically significant response to the dose administered. The PR and QRS intervals lengthened and the other intervals shortened (although to a lesser degree). The compound was well tolerated, with mild symptoms only at higher doses. Bioavailability was studied in 12 male volunteers, with each receiving 2.0 mg/kg of bidisomide, both orally and intravenously, in an open‐label crossover trial. After a 10‐minute zero‐order intravenous infusion, bidisomide plasma levels could best be described in terms of a three‐compartment pharmacokinetic model with the mean half‐life values of α, β, and γ phases of 0.12, 1.77, and 12.3 hours, respectively. The mean absolute oral bioavailability was 43%. (CLIN PHARMACOL THER 1992;51:371‐78.) Clinical Pharmacology and Therapeutics (1992) 51, 371–378; doi: 10.1038/clpt.1992.36