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Kinetics of the oral antiarrhythmie lidocaine congener, tocainide
Author(s) -
Lalka David,
Meyer Melvin B.,
Duce Benjamin R.,
Elvin Alfred T.
Publication year - 1976
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 - 10.1002/cpt1976196757
Subject(s) - pharmacokinetics , bioavailability , lidocaine , chemistry , absorption (acoustics) , pharmacology , sodium bicarbonate , area under the curve , anesthesia , medicine , physics , acoustics
Tocainide, a primary amine analogue of lidocaine, is effective against some experimental and clinical arrhythmias. Its pharmacokinetic behavior was studied in 6 healthy male subjects. Peak blood levels (C B max) and area under the blood concentration‐time curve (AUC) were linearly related to dose with slopes of 0.0067 mcg/ml and 6 min mcg/ml per milligram of dose, respectively. Renal clearance of tocainide averaged 59 ml/min when urinary pH was uncontrolled or acidified, while it was reduced to 13 ml/min during intense sodium bicarbonate loading. Blood levels following intravenous infusion were well described by a 2‐compartment open model with a volume of the central compartment of 0.92 L/kg. The t 1/2β was 11 hr and total body clearance was 166 ml/min. Loo‐Riegelman analysis of the absorption rate did not allow unequivocal assignment of an “order” to the absorption process. Bioavailability approached 100%. Administration of drug 5 min after a test meal suppressed C B max 40% but minimally affected AUC. Approximately 50% of the drug was found to be plasma protein bound at clinically effective concentrations.