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 alpha, beta, and gamma phases of 0.12, 1.77, and 12.3 hours, respectively. The mean absolute oral bioavailability was 43%.
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R L
RL
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Wharton
J M
JM
Wilkinson
W E
WE
Friedman
I M
IM
Claypool
W D
WD
Karim
A
A
Kowalski
K G
KG
McDonald
S J
SJ
Gardiner
P
P
Pritchett
E L
EL
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
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; C061991:bidisomide