Tocainide

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

Tocainide

Clinical data
Trade names	Tonocard
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a601248
ATC code	C01BB03 (WHO)
Pharmacokinetic data
Bioavailability	0.9-1 (oral)
Protein binding	10-20%
Metabolism	glucuronidation (primary)
Elimination half-life	9-14 R, 13-20 S
Excretion	30-50% urine (unchanged)
Identifiers
IUPAC name N-(2,6-dimethylphenyl)alaninamide
CAS Number	41708-72-9 Y
PubChem CID	38945
IUPHAR/BPS	7309
DrugBank	DB01056 Y
ChemSpider	35632 Y
UNII	27DXO59SAN
KEGG	D06172 Y
ChEBI	CHEBI:9611 Y
ChEMBL	ChEMBL1762 Y
CompTox Dashboard (EPA)	DTXSID9040766
ECHA InfoCard	100.050.441
Chemical and physical data
Formula	C11H16N2O
Molar mass	192.262 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C(Nc1c(cccc1C)C)C(N)C
InChI 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
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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]