Tocainide Explained

Tocainide (Tonocard) 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.^[1] Tocainide's oral bioavailability is almost 100%.^[2] Plasma half-life generally lasts for 11.5-15.5 hours (13.5 ± 2 hours^[3]). In the blood, tocainide is 10-20% protein bound.^[4] 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 (without kidneys) 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,^[5] 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.^[6] Tocainide decreases plasma clearance of theophylline.^[7]

Further reading

• Book: Burton ME . Applied Pharmacokinetics & Pharmacodynamics: Principles of Therapeutic Drug Monitoring . 2006 . Lippincott Williams & Wilkins . 59148565 . 978-0-7817-4431-7.

Notes and References

1. Tricarico D, Fakler B, Spittelmeister W, Ruppersberg JP, Stützel R, Franchini C, Tortorella V, Conte-Camerino D, Rüdel R . Stereoselective interaction of tocainide and its chiral analogs with the sodium channels in human myoballs . Pflügers Archiv . 418 . 3 . 234–237 . April 1991 . 1649990 . 10.1007/BF00370521 . 24456292 .
2. Kutalek SP, Morganroth J, Horowitz LN . Tocainide: a new oral antiarrhythmic agent . Annals of Internal Medicine . 103 . 3 . 387–391 . September 1985 . 3927807 . 10.7326/0003-4819-103-3-387 .
3. Winkle RA, Meffin PJ, Fitzgerald JW, Harrison DC . Clinical efficacy and pharmacokinetics of a new orally effective antiarrhythmic, tocainide . Circulation . 54 . 6 . 885–889 . December 1976 . 791536 . 10.1161/01.CIR.54.6.885 . free .
4. Web site: Kidney Disease Program (KDP) . dead . 2023-12-12 . https://web.archive.org/web/20231212181858/https://kdpnet.kdp.louisville.edu/drugbook/adult/?leaf=4314 . 2023-12-12 . University of Louisville.
5. Studies on the metabolism of tocainide in humans . University of British Columbia . 1987 . Kwok DW .
6. Rice TL, Patterson JH, Celestin C, Foster JR, Powell JR . Influence of rifampin on tocainide pharmacokinetics in humans . Clinical Pharmacy . 8 . 3 . 200–205 . March 1989 . 2495879 .
7. Loi CM, Wei X, Parker BM, Korrapati MR, Vestal RE . The effect of tocainide on theophylline metabolism . British Journal of Clinical Pharmacology . 35 . 4 . 437–440 . April 1993 . 8485025 . 1381557 . 10.1111/j.1365-2125.1993.tb04163.x .