Chemistry:Tocainide

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Short description: Chemical compound
Tocainide
File:Tocainide.svg
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
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC11H16N2O
Molar mass192.262 g·mol−1
3D model (JSmol)
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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. ↑ Boyes RN, Byrnes EW, "Antiarrhythmisch Wirksame Verbindung, Verfahren zu Deren Herstellung und Deren Verwendung", DE patent 2235745, issued 1972, assigned to Astra Pharmaceutical Products Inc.
  2. ↑ "Primary Amino Acylanilides Methods of Making the Same and Use as Antiarrhythmic Drugs" GB patent 1461602, issued 1974, assigned to Astra Pharmaceutical Products Inc.
  3. ↑ Boyes RN, Duce BR, Smith EM, Byrnes EW, "Primaeraminoacylanilide, Verfahren zu Deren Herstellung und Sie Enthaltende Arzneimittel", DE patent 2400540, issued 1974, assigned to Astra Pharmaceutical Products Inc.
  4. ↑ "New antiarrhythmic agents. 1. Primary alpha-amino anilides". Journal of Medicinal Chemistry 22 (10): 1171–6. October 1979. 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. et al. (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. https://doi.org/10.1007/BF00370521. 
  6. ↑ 6.0 6.1 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. https://pubmed.ncbi.nlm.nih.gov/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. https://www.ahajournals.org/doi/10.1161/01.CIR.54.6.885. 
  8. ↑ 8.0 8.1 8.2 "Kidney Disease Program (KDP)". University of Louisville. https://kdpnet.kdp.louisville.edu/drugbook/adult/?leaf=4314. 
  9. ↑ 9.0 9.1 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. https://pubmed.ncbi.nlm.nih.gov/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. PMID 8485025. 

Further reading






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