Details of the Drug

General Information of Drug (ID: DMYNMDP)

• Drug Name: Tocainide
• Synonyms: Taquidil; Tocainida; Tocainidum; Tonocard; Astra W 36095; Tocainida [INN-Spanish]; Tocainidum [INN-Latin]; W-36095; Tocainide (USAN/INN); Tocainide [USAN:BAN:INN]; Alanyl-2,6-xylidide; N-(2,6-dimethylphenyl)alaninamide; (-)-2-Amino-N-(2,6-dimethylphenyl)propanamide; 2-AMINO-N-(2,6-DIMETHYLPHENYL)PROPANAMIDE; 2-Amino-2',6'-propionoxylidide; 2-Amino-N-(2,6-dimethylphenyl)propionamid

Indication

Disease Entry	ICD 11	Status	REF
Ventricular arrhythmias	BC71	Approved	[1], [2]

• Therapeutic Class: Antiarrhythmic Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 192.26
  Topological Polar Surface Area (xlogp); 0.8
  Rotatable Bond Count (rotbonds); 2
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
  Bioavailability: 89% of drug becomes completely available to its intended biological destination(s) [4]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 2.2 mL/min/kg [5]
  Elimination: 38% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 15 hours [5]
  Metabolism: The drug is metabolized via the hepatic [6]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.87% [5]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 1.8 L/kg [5]
  Water Solubility: The ability of drug to dissolve in water is measured as 10 mg/mL [3]
• Chemical Identifiers:
  Formula: C11H16N2O
  IUPAC Name: 2-amino-N-(2,6-dimethylphenyl)propanamide
  Canonical SMILES: CC1=C(C(=CC=C1)C)NC(=O)C(C)N
  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)
  InChIKey: BUJAGSGYPOAWEI-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 38945
  ChEBI ID: CHEBI:9611
  CAS Number: 41708-72-9
  DrugBank ID: DB01056
  TTD ID: D01PJR
  INTEDE ID: DR1607

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
E3 ubiquitin-protein ligase COP1 (RFWD2)	TT05DLS	COP1_HUMAN	Modulator	[7]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 1A2 (CYP1A2) Main DME	DEJGDUW	CP1A2_HUMAN	Substrate	[8]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Tocainide (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Tocainide and Ocrelizumab.	Multiple sclerosis [8A40]	[20]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Tocainide and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[21]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Tocainide and Valganciclovir.	Virus infection [1A24-1D9Z]	[22]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7309).
• [2] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 018257.
• [3] BDDCS applied to over 900 drugs
• [4] Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
• [5] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [6] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] The effect of tocainide on theophylline metabolism. Br J Clin Pharmacol. 1993 Apr;35(4):437-40.
• [9] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [10] Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Mol Carcinog. 2004 Jul;40(3):180-8.
• [11] Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
• [12] Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
• [13] PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
• [14] The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
• [15] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [16] The influence of metabolic gene polymorphisms on urinary 1-hydroxypyrene concentrations in Chinese coke oven workers. Sci Total Environ. 2007 Aug 1;381(1-3):38-46.
• [17] Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
• [18] Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
• [19] Barucainide, a novel class Ib antiarrhythmic agent with a slow kinetic property: electrophysiologic observations in isolated canine and rabbit cardiac muscle. Am Heart J. 1990 May;119(5):1050-60.
• [20] Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
• [21] Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
• [22] Cerner Multum, Inc. "Australian Product Information.".