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 interactionsedit
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]
Referencesedit
^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.
^ abKutalek 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.
^ abc. University of Louisville. Archived from the original on 2023-12-12. Retrieved 2023-12-12.
^ abKwok 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. PMC1381557. PMID 8485025.
Further readingedit
Burton ME (2006). Applied Pharmacokinetics & Pharmacodynamics: Principles of Therapeutic Drug Monitoring. Lippincott Williams & Wilkins. ISBN978-0-7817-4431-7. OCLC 59148565.
tocainide, tonocard, class, antiarrhythmic, agent, longer, sold, united, states, clinical, datatrade, namestonocardahfs, drugs, commicromedex, detailed, consumer, informationmedlineplusa601248atc, codec01bb03, pharmacokinetic, databioavailability0, oral, prote. Tocainide Tonocard is a class Ib antiarrhythmic agent It is no longer sold in the United States TocainideClinical dataTrade namesTonocardAHFS Drugs comMicromedex Detailed Consumer InformationMedlinePlusa601248ATC codeC01BB03 WHO Pharmacokinetic dataBioavailability0 9 1 oral Protein binding10 20 Metabolismglucuronidation primary Elimination half life9 14 R 13 20 SExcretion30 50 urine unchanged IdentifiersIUPAC name N 2 6 dimethylphenyl alaninamideCAS Number41708 72 9 YPubChem CID38945IUPHAR BPS7309DrugBankDB01056 YChemSpider35632 YUNII27DXO59SANKEGGD06172 YChEBICHEBI 9611 YChEMBLChEMBL1762 YCompTox Dashboard EPA DTXSID9040766ECHA InfoCard100 050 441Chemical and physical dataFormulaC 11H 16N 2OMolar mass192 262 g mol 13D model JSmol Interactive imageSMILES O C Nc1c cccc1C C C N CInChI 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 YKey BUJAGSGYPOAWEI UHFFFAOYSA N Y verify Contents 1 Synthesis 2 Pharmacokinetics 3 Drug interactions 4 References 5 Further reading 6 External linksSynthesis edit nbsp Tocainide synthesis 1 2 3 4 Pharmacokinetics editTocainide 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 editRifampicin 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 edit 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 Stutzel R Franchini C et al April 1991 Stereoselective interaction of tocainide and its chiral analogs with the sodium channels in human myoballs Pflugers 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 Further reading editBurton ME 2006 Applied Pharmacokinetics amp Pharmacodynamics Principles of Therapeutic Drug Monitoring Lippincott Williams amp Wilkins ISBN 978 0 7817 4431 7 OCLC 59148565 External links editMedlinePlus DrugInfo medmaster a685030 nbsp This drug article relating to the cardiovascular system is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Tocainide amp oldid 1221963653, wikipedia, wiki, book, books, library,
