Tocainide

Tocainide is a class Ib antiarrhythmic agent. It is no longer sold in the United States.

Pharmacokinetics

Tocainide is a lidocaine derivative, that undergoes very less first pass metabolism. It occurs as two enantiomers. The R isomer is three times more potent than the S isomer. Tocainide's oral bioavailability is almost 100%. Plasma half-life generally lasts for 11.5-15.5 hours. In the blood, tocainide is 10-20% protein bound. The volume of distribution is 2.8-3.2 L/kg. 31-45% is excreted unchanged in the urine. The more active R-isomer is cleared faster in anephric patients or those with severe kidney dysfunction. The main metabolite is tocainide carbamoyl ester glucuronlde.

Drug interactions

Rifampicin increases conversion of tocainide into its main metabolite, tocainide carbamoyl ester glucuronlde, by inducing the glucuronosyl transferase enzyme that catalyzes glucuronidation of tocainide to produce that metabolite. Rifampicin also increases elimination rate and decreases oral clearance of tocainide. Tocainide decreases plasma clearance of theophylline.

Pharmacokinetics

Oral bioavailability is high, with low protein binding and renal excretion of a substantial unchanged fraction; metabolism proceeds largely via glucuronidation. Reported plasma half-life values are roughly in the 9–20 hour range, with known stereoselective differences between enantiomers.

History and status

Tocainamide emerged in the 1970s as an orally effective alternative to lidocaine for ventricular arrhythmias, with early uncontrolled and controlled studies in refractory patients. Accumulating reports of bone-marrow toxicity and other serious adverse events led to declining use and eventual withdrawal from some markets; in the United States, tocainide products were removed in 2003.