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Pirmenol kinetics and effective oral dose
Author(s) -
Hammill Stephen C,
Shand David G,
Harrell Frank E,
Zimmerman Jane M,
Reiter Michael J,
Verghese Chacko,
Pritchett Edward L C
Publication year - 1982
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.1982.224
Subject(s) - medicine , placebo , qrs complex , crossover study , qt interval , pr interval , heart rate , bioavailability , cardiology , blood pressure , anesthesia , pharmacology , alternative medicine , pathology
The oral form of pirmenol has not been administered to man. Pirmenol was given by mouth to eight patients with chronic, stable premature ventricular beats (PVBs) to determine effective dose and kinetics. The patients were evaluated with a dose‐ranging protocol followed by a double‐blind, crossover, placebo‐controlled study of doses that were effective during dose ranging. Oral doses of 150 to 250 mg induced at least 90% suppression of PVBs 18 of the 19 times they were administered during both protocols. During the double‐blind experiment, a single oral dose of pirmenol suppressed 95 ± 8% PVBs/hr (mean ± SD) for 3 consecutive hr, while placebo suppressed 4 ± 42% PVBs/hr (P < 0.01). A 90% or greater reduction in PVBs persisted for a median of 6 hr (range 1 to 8 hr). The range of plasma pirmenol concentrations associated with an at least 90% reduction in PVBs was 0.7 to 2.0 μg/ml. Median half‐life (t½) was 9.3 hr (range 6.0 to 12.4) with 86.6 ± 2.4% protein binding and 82.6 ± 23.6% bioavailability. At peak drug level there was lengthening of the QTc interval (0.036 sec, P <0.05), but no change in heart rate, blood pressure, PR interval or QRS duration, or symptoms. In this single‐dose study, pirmenol effectively reduced PVBs, had a relatively long t½, and was minimally toxic. Clinical Pharmacology and Therapeutics (1982) 32 , 686–691; doi: 10.1038/clpt.1982.224