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Comparison of the pharmacodynamic effects of intravenous and oral propafenone
Author(s) -
Haefeli Emil Walter,
Vozeh Samuel,
Ha HuyRiêm,
Follath Ferenc
Publication year - 1990
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.1990.146
Subject(s) - propafenone , pharmacodynamics , pharmacokinetics , medicine , metabolite , pharmacology , active metabolite , oral administration , dosing , oral dose , anesthesia , atrial fibrillation
The effect of propafenone and its major metabolite 5‐hydroxy‐propafenone on ECG intervals was investigated in eight healthy extensive metabolizers after single oral (300 to 450 mg) and intravenous (35 to 50 mg) doses of propafenone in a single‐blind randomized trial. Peak serum concentrations were 278 ± 233 ng/ml (oral) and 295 ±131 ng/ml (intravenous). After oral administration peak 5‐hydroxy‐propafenone levels were 194 ± 65 ng/ml, whereas after intravenous dosing no metabolite was detected, except in one subject. Serum concentrations were related to effects by linear regression including a hypothetical effect‐site compartment in a pharmacokinetic‐pharmacodynamic model. Significant prolongations of ECG intervals were found in both sequences. Comparison of the two concentration‐effect data sets (intravenous, oral) revealed an additive effect of 5‐hydroxy‐propafenone in four of eight subjects for PQ interval and seven of eight subjects for QRS duration. We conclude that 5‐hydroxy‐propafenone exerts pharmacologic activity and could thus contribute to the antiarrhythmic effect of propafenone. Clinical Pharmacology and Therapeutics (1990) 48, 245–254; doi: 10.1038/clpt.1990.146