Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Tocainide: Difference between pages

{{Short description|Chemical compound}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

| verifiedrevid = 470611261

| tradename = Tonocard

| pregnancy_category =

| legal_status =

| routes_of_administration =

| IUPHAR_ligand = 7309

| ATC_supplemental =

| ChEBI_Ref = {{ebicite|correct|EBI}}

| C=11 | H=16 | N=2 | O=1

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

==Synthesis==

[[File:Tocainide synthesis.png|thumb|center|400px|Tocainide synthesis:<ref>{{cite patent | country = DE | number = 2235745 | title = Antiarrhythmisch Wirksame Verbindung, Verfahren zu Deren Herstellung und Deren Verwendung | gdate = 1972 | inventor = Boyes RN, Byrnes EW | assign1 = Astra Pharmaceutical Products Inc. }}</ref><ref>{{cite patent | title = Primary Amino Acylanilides Methods of Making the Same and Use as Antiarrhythmic Drugs | assign1 = Astra Pharmaceutical Products Inc. | country = GB | number = 1461602 | gdate = 1974 }}</ref><ref>{{cite patent | title = Primaeraminoacylanilide, Verfahren zu Deren Herstellung und Sie Enthaltende Arzneimittel | inventor = Boyes RN, Duce BR, Smith EM, Byrnes EW | country = DE | number = 2400540 | gdate = 1974 | assign1 = Astra Pharmaceutical Products Inc. }}</ref><ref>{{cite journal | vauthors = Byrnes EW, McMaster PD, Smith ER, Blair MR, Boyes RN, Duce BR, Feldman HS, Kronberg GH, Takman BH, Tenthorey PA | title = New antiarrhythmic agents. 1. Primary alpha-amino anilides | journal = Journal of Medicinal Chemistry | volume = 22 | issue = 10 | pages = 1171–1176 | date = October 1979 | pmid = 513064 | doi = 10.1021/jm00196a005 }}</ref>]]

==Pharmacokinetics==

Tocainide is a [[lidocaine]] derivative, that undergoes very less [[first pass metabolism]]. It occurs as two [[enantiomer]]s. The R isomer is three times more potent than the S isomer.<ref>{{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 }}</ref> Tocainide's oral bioavailability is almost 100%.<ref name="Kutalek1985">{{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 }}</ref> Plasma half-life generally lasts for 11.5-15.5 hours (13.5 ± 2 hours<ref>{{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 }}</ref>). In the blood, tocainide is 10-20% protein bound.<ref name="UofL">{{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}}</ref><ref name="Kutalek1985" /> The volume of distribution is 2.8-3.2 L/kg.<ref name="UofL" /> 31-45% is excreted unchanged in the urine.<ref name="UofL" /> 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.<ref name="Kwok1987" />

==Drug interactions==

[[Rifampicin]] increases conversion of tocainide into its main metabolite, tocainide carbamoyl ester glucuronlde,<ref name="Kwok1987">{{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 }}</ref> 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.<ref>{{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/ }}</ref> Tocainide decreases [[plasma clearance]] of theophylline.<ref>{{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 }}</ref>

== References ==

{{Reflist}}

== Further reading ==

{{refbegin}}

* {{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}}

{{refend}}

== External links ==

*{{MedlinePlusDrugInfo|medmaster|a685030}}

{{Sodium channel blockers}}

{{Antiarrhythmic agents}}

[[Category:Antiarrhythmic agents]]

[[Category:Sodium channel blockers]]

[[Category:Anilides]]

{{cardiovascular-drug-stub}}