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Pharmacodynamics and pharmacokinetics of oral pirmenol
Author(s) -
Ellenbogen Kenneth A,
Roark Steven F,
Sintetos Anthony L,
Smith Mark S,
McCarthy Elizabeth A,
Smith William M,
Kates Robert E,
Pritchett Edward L C
Publication year - 1987
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1987.170
Subject(s) - medicine , pharmacodynamics , pharmacokinetics , washout , plasma concentration , anesthesia
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 µg/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 suppresssion. Clinical Pharmacology and Therapeutics (1987) 42, 405–410; doi: 10.1038/clpt.1987.170