Tocainide
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| Clinical data | |
|---|---|
| Trade names | Tonocard |
| Other names | Tocainamide |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
| MedlinePlus | a601248 |
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| 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) |
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| E number | {{#property:P628}} |
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| ECHA InfoCard | {{#property:P2566}}Lua error in Module:EditAtWikidata at line 29: attempt to index field 'wikibase' (a nil value). |
| Chemical and physical data | |
| Formula | C11H16N2O |
| Molar mass | 192.262 g·mol−1 |
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Tocainide (Tonocard) is a class Ib antiarrhythmic agent. It is no longer sold in the United States.
Synthesis
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Pharmacokinetics
[edit | edit source]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
[edit | edit source]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]
Pharmacokinetics
[edit | edit source]Oral bioavailability is high (near complete), with low protein binding (≈10–20%) and renal excretion of a substantial unchanged fraction; metabolism proceeds largely via glucuronidation. Reported plasma half-life values are roughly in the 9–20 hour range, with known stereoselective differences between enantiomers.[12][13]
History and status
[edit | edit source]Tocainamide (tocainide) emerged in the 1970s as an orally effective alternative to lidocaine for ventricular arrhythmias, with early uncontrolled and controlled studies in refractory patients.[14][15] Accumulating reports of bone-marrow toxicity and other serious adverse events led to declining use and eventual withdrawal from some markets; in the United States, tocainide products were removed in 2003.[16][17]
See also
[edit | edit source]References
[edit | edit source]- ^ DE 2235745, Boyes RN, Byrnes EW, "Antiarrhythmisch Wirksame Verbindung, Verfahren zu Deren Herstellung und Deren Verwendung", issued Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value)., assigned to Astra Pharmaceutical Products Inc.
- ^ GB 1461602, "Primary Amino Acylanilides Methods of Making the Same and Use as Antiarrhythmic Drugs", issued Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value)., 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 Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value)., assigned to Astra Pharmaceutical Products Inc.
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Further reading
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