Pharmacodynamics and pharmacokinetics of oral pirmenol.
The efficacy, pharmacokinetics, and pharmacodynamics of pirmenol, a class Ia antiarrhythmic agent, were studied in patients with frequent symptomatic premature ventricular complexes (PVCs). Pirmenol was given every 12 hours to eight patients in a dose-ranging protocol, and median PVC suppression of 94% (range 72% to 100%) was achieved. The median effective pirmenol dose was 300 mg/day (range 200 to 500 mg/day), and mean (+/- SD) trough plasma pirmenol concentration at the effective dose was 0.98 +/- 0.29 micrograms/ml. The mean half-life of elimination was 10.5 +/- 2 hours. There was considerable overlap among patients with respect to plasma pirmenol concentration and times at which PVC frequency returned to 25%, 50%, and 75% of baseline during drug washout trials. Altering pirmenol's dose interval (while maintaining a constant daily dose) from 12 to 6 hours did not improve drug efficacy. Pirmenol was given to seven patients for long-term therapy (24 to 44 months). Median PVC suppression at 24 months was 70%. Pirmenol is safe and well tolerated, and it can be administered twice daily for PVC suppression.
Ellenbogen
K A
KA
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Roark
S F
SF
Sintetos
A L
AL
Smith
M S
MS
McCarthy
E A
EA
Smith
W M
WM
Kates
R E
RE
Pritchett
E L
EL
D000284:Administration, Oral; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010880:Piperidines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; C024318:pirmenol