Tocainide

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

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) Y
  • Key:BUJAGSGYPOAWEI-UHFFFAOYSA-N Y
  (verify)

Synthesis

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.
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Further reading
  • Lua error in Module:Citation/CS1/Configuration at line 2058: attempt to index a boolean value.
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