Tocainide

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.^[5] Tocainide's oral bioavailability is almost 100%.^[6] Plasma half-life generally lasts for 11.5-15.5 hours (13.5 ± 2 hours^[7]). In the blood, tocainide is 10-20% protein bound.^[8][6] The volume of distribution is 2.8-3.2 L/kg.^[8] 31-45% is excreted unchanged in the urine.^[8] The more active R-isomer is cleared faster in anephric patients (without kidneys) or those with severe kidney dysfunction. The main metabolite is tocainide carbamoyl ester glucuronlde.^[9]

Rifampicin increases conversion of tocainide into its main metabolite, tocainide carbamoyl ester glucuronlde,^[9] 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.^[10] Tocainide decreases plasma clearance of theophylline.^[11]

Oral bioavailability is high (near complete), with low protein binding (≈10–20%) 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.^[12][13]

Tocainamide (tocainide) emerged in the 1970s as an orally effective alternative to lidocaine for ventricular arrhythmias, with early uncontrolled and controlled studies in refractory patients.^[14][15] 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.^[16][17]

• Class I antiarrhythmic
• Mexiletine
• Lidocaine