Kinetics of the oral antiarrhythmic lidocaine congener, tocainide.
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 (CB 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 1/2 beta 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 CB max 40% but minimally affected AUC. Approximately 50% of the drug was found to be plasma protein bound at clinically effective concentrations.
D000284:Administration, Oral; D000328:Adult; D000813:Anilides / Q000378:metabolism*; D000889:Anti-Arrhythmia Agents / Q000378:metabolism*; D001639:Bicarbonates / Q000494:pharmacology; D001682:Biological Availability; D004334:Drug Administration Schedule; D005021:Ethylamines / Q000378:metabolism; D005502:Food; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D007408:Intestinal Absorption / Q000187:drug effects; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D013997:Time Factors
D000813:Anilides; D000889:Anti-Arrhythmia Agents; D001639:Bicarbonates; D005021:Ethylamines; D008012:Lidocaine