tocainide

File:Tocainide synthesis.png

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.{{cite journal | vauthors = Tricarico D, Fakler B, Spittelmeister W, Ruppersberg JP, Stützel R, Franchini C, Tortorella V, Conte-Camerino D, Rüdel R | title = Stereoselective interaction of tocainide and its chiral analogs with the sodium channels in human myoballs | journal = Pflügers Archiv | volume = 418 | issue = 3 | pages = 234–237 | date = April 1991 | pmid = 1649990 | doi = 10.1007/BF00370521 | s2cid = 24456292 }} Tocainide's oral bioavailability is almost 100%.{{cite journal | vauthors = Kutalek SP, Morganroth J, Horowitz LN | title = Tocainide: a new oral antiarrhythmic agent | journal = Annals of Internal Medicine | volume = 103 | issue = 3 | pages = 387–391 | date = September 1985 | pmid = 3927807 | doi = 10.7326/0003-4819-103-3-387 }} Plasma half-life generally lasts for 11.5-15.5 hours (13.5 ± 2 hours{{cite journal | vauthors = Winkle RA, Meffin PJ, Fitzgerald JW, Harrison DC | title = Clinical efficacy and pharmacokinetics of a new orally effective antiarrhythmic, tocainide | journal = Circulation | volume = 54 | issue = 6 | pages = 885–889 | date = December 1976 | pmid = 791536 | doi = 10.1161/01.CIR.54.6.885 | doi-access = free }}). In the blood, tocainide is 10-20% protein bound.{{Cite web |title=Kidney Disease Program (KDP) |url=https://kdpnet.kdp.louisville.edu/drugbook/adult/?leaf=4314 |url-status=dead |archive-date=2023-12-12 |archive-url=https://web.archive.org/web/20231212181858/https://kdpnet.kdp.louisville.edu/drugbook/adult/?leaf=4314 |access-date=2023-12-12 |publisher=University of Louisville}} The volume of distribution is 2.8-3.2 L/kg. 31-45% is excreted unchanged in the urine. 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.

Rifampicin increases conversion of tocainide into its main metabolite, tocainide carbamoyl ester glucuronlde,{{Cite thesis |title=Studies on the metabolism of tocainide in humans |url=https://open.library.ubc.ca/soa/cIRcle/collections/ubctheses/831/items/1.0096967 |publisher=University of British Columbia |date=1987 | vauthors = Kwok DW }} 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.{{cite journal | vauthors = Rice TL, Patterson JH, Celestin C, Foster JR, Powell JR | title = Influence of rifampin on tocainide pharmacokinetics in humans | journal = Clinical Pharmacy | volume = 8 | issue = 3 | pages = 200–205 | date = March 1989 | pmid = 2495879 | url = https://pubmed.ncbi.nlm.nih.gov/2495879/ }} Tocainide decreases plasma clearance of theophylline.{{cite journal | vauthors = Loi CM, Wei X, Parker BM, Korrapati MR, Vestal RE | title = The effect of tocainide on theophylline metabolism | journal = British Journal of Clinical Pharmacology | volume = 35 | issue = 4 | pages = 437–440 | date = April 1993 | pmid = 8485025 | pmc = 1381557 | doi = 10.1111/j.1365-2125.1993.tb04163.x }}

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• {{cite book | vauthors = Burton ME |url=https://books.google.com/books?id=n6PQxWEaXuwC |title=Applied Pharmacokinetics & Pharmacodynamics: Principles of Therapeutic Drug Monitoring |date=2006 |publisher=Lippincott Williams & Wilkins |oclc=59148565 |isbn=978-0-7817-4431-7}}

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{{Sodium channel blockers}}

{{Antiarrhythmic agents}}

Category:Antiarrhythmic agents

Category:Sodium channel blockers

Category:Anilides

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