title: Bidisomide (SC-40230), a new antiarrhythmic agent: initial study of tolerability and pharmacokinetics.
abstract: 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 alpha, beta, and gamma phases of 0.12, 1.77, and 12.3 hours, respectively. The mean absolute oral bioavailability was 43%.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, NC 27710.
authors.forename: R L
authors.initials: RL
authors.lastname: Page
authors.forename: J M
authors.initials: JM
authors.lastname: Wharton
authors.forename: W E
authors.initials: WE
authors.lastname: Wilkinson
authors.forename: I M
authors.initials: IM
authors.lastname: Friedman
authors.forename: W D
authors.initials: WD
authors.lastname: Claypool
authors.forename: A
authors.initials: A
authors.lastname: Karim
authors.forename: K G
authors.initials: KG
authors.lastname: Kowalski
authors.forename: S J
authors.initials: SJ
authors.lastname: McDonald
authors.forename: P
authors.initials: P
authors.lastname: Gardiner
authors.forename: E L
authors.initials: EL
authors.lastname: Pritchett
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011897:Random Allocation
chemical_list: D000889:Anti-Arrhythmia Agents; D010880:Piperidines; C061991:bidisomide