Tocainide

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 ;
PubChem CID	38945;
IUPHAR/BPS	7309;
DrugBank	DB01056 ;
ChemSpider	35632 ;
UNII	27DXO59SAN;
KEGG	D06172 ;
ChEBI	CHEBI:9611 ;
ChEMBL	ChEMBL1762 ;
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) ; Key:BUJAGSGYPOAWEI-UHFFFAOYSA-N ;
	(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

^ DE 2235745, Boyes RN, Byrnes EW, "Antiarrhythmisch Wirksame Verbindung, Verfahren zu Deren Herstellung und Deren Verwendung", issued 1972, assigned to Astra Pharmaceutical Products Inc.
^ GB 1461602, "Primary Amino Acylanilides Methods of Making the Same and Use as Antiarrhythmic Drugs", issued 1974, assigned to Astra Pharmaceutical Products Inc.
^ 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.
^ 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): 1171–1176. doi:10.1021/jm00196a005. PMID 513064.
^ Tricarico D, Fakler B, Spittelmeister W, Ruppersberg JP, Stützel R, Franchini C, et al. (April 1991). "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. PMID 1649990. S2CID 24456292.
^ ^a ^b Kutalek SP, Morganroth J, Horowitz LN (September 1985). "Tocainide: a new oral antiarrhythmic agent". Annals of Internal Medicine. 103 (3): 387–391. doi:10.7326/0003-4819-103-3-387. PMID 3927807.
^ Winkle RA, Meffin PJ, Fitzgerald JW, Harrison DC (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. PMID 791536.
^ ^a ^b ^c "Kidney Disease Program (KDP)". University of Louisville. Archived from the original on 2023-12-12. Retrieved 2023-12-12.
^ ^a ^b Kwok DW (1987). Studies on the metabolism of tocainide in humans (Thesis). University of British Columbia.
^ Rice TL, Patterson JH, Celestin C, Foster JR, Powell JR (March 1989). "Influence of rifampin on tocainide pharmacokinetics in humans". Clinical Pharmacy. 8 (3): 200–205. PMID 2495879.
^ Loi CM, Wei X, Parker BM, Korrapati MR, Vestal RE (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. PMC 1381557. PMID 8485025.