Tocainide
Clinical data
Trade namesTonocard
AHFS/Drugs.comMicromedex Detailed Consumer Information
MedlinePlusa601248
ATC code
Pharmacokinetic data
Bioavailability0.9-1 (oral)
Protein binding10-20%
Metabolismglucuronidation (primary)
Elimination half-life9-14 R, 13-20 S
Excretion30-50% urine (unchanged)
Identifiers
  • N-(2,6-dimethylphenyl)alaninamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.050.441
Chemical and physical data
FormulaC11H16N2O
Molar mass192.262 g·mol−1
3D model (JSmol)
  • O=C(Nc1c(cccc1C)C)C(N)C
  • InChI=1S/C11H16N2O/c1-7-5-4-6-8(2)10(7)13-11(14)9(3)12/h4-6,9H,12H2,1-3H3,(H,13,14) checkY
  • Key:BUJAGSGYPOAWEI-UHFFFAOYSA-N checkY
  (verify)

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

Synthesis

Tocainide synthesis:[1][2][3][4]

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.[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]

Drug interactions

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]

References

  1. ↑ DE 2235745, Boyes RN, Byrnes EW, "Antiarrhythmisch Wirksame Verbindung, Verfahren zu Deren Herstellung und Deren Verwendung", issued 1972, assigned to Astra Pharmaceutical Products Inc.
  2. ↑ GB 1461602, "Primary Amino Acylanilides Methods of Making the Same and Use as Antiarrhythmic Drugs", issued 1974, assigned to Astra Pharmaceutical Products Inc.
  3. ↑ DE 2400540, Boyes RN, Duce BR, Smith EM, Byrnes EW, "Primaeraminoacylanilide, Verfahren zu Deren Herstellung und Sie Enthaltende Arzneimittel", issued 1974, assigned to Astra Pharmaceutical Products Inc.
  4. ↑ Byrnes EW, McMaster PD, Smith ER, Blair MR, Boyes RN, Duce BR, et al. (October 1979). "New antiarrhythmic agents. 1. Primary alpha-amino anilides". Journal of Medicinal Chemistry. 22 (10): 1171–6. doi:10.1021/jm00196a005. PMID 513064.
  5. ↑ Tricarico, D.; Fakler, B.; Spittelmeister, W.; Ruppersberg, J. P.; Stützel, R.; Franchini, C.; Tortorella, V.; Conte-Camerino, D.; Rüdel, R. (1991-04-01). "Stereoselective interaction of tocainide and its chiral analogs with the sodium channels in human myoballs". Pflügers Archiv. 418 (3): 234–237. doi:10.1007/BF00370521. ISSN 1432-2013. PMID 1649990. S2CID 24456292.
  6. 1 2 Kutalek, S. P.; Morganroth, J.; Horowitz, L. N. (September 1985). "Tocainide: a new oral antiarrhythmic agent". Annals of Internal Medicine. 103 (3): 387–391. doi:10.7326/0003-4819-103-3-387. ISSN 0003-4819. PMID 3927807.
  7. ↑ Winkle, R A; Meffin, P J; Fitzgerald, J W; Harrison, D C (December 1976). "Clinical efficacy and pharmacokinetics of a new orally effective antiarrhythmic, tocainide". Circulation. 54 (6): 885–889. doi:10.1161/01.CIR.54.6.885. ISSN 0009-7322. PMID 791536.
  8. 1 2 3 "Kidney Disease Program (KDP)". University of Louisville. Archived from the original on 2023-12-12. Retrieved 2023-12-12.
  9. 1 2 Kwok, David W. K. (1987). Studies on the metabolism of tocainide in humans (Thesis). University of British Columbia.
  10. ↑ Rice, T. L.; Patterson, J. H.; Celestin, C.; Foster, J. R.; Powell, J. R. (March 1989). "Influence of rifampin on tocainide pharmacokinetics in humans". Clinical Pharmacy. 8 (3): 200–205. ISSN 0278-2677. PMID 2495879.
  11. ↑ Loi, C. M.; Wei, X.; Parker, B. M.; Korrapati, M. R.; Vestal, R. E. (April 1993). "The effect of tocainide on theophylline metabolism". British Journal of Clinical Pharmacology. 35 (4): 437–440. doi:10.1111/j.1365-2125.1993.tb04163.x. ISSN 0306-5251. PMC 1381557. PMID 8485025.

Further reading




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