Details of the Drug

General Information of Drug (ID: DM4IF32)

Drug Name
Pyrazinamide
Synonyms
Aldinamid; Aldinamide; Braccopiral; Corsazinmid; Dipimide; Eprazin; Farmizina; Isopas; Lynamide; Novamid; Pezetamid; Pharozinamide; Piraldina; Pirazimida; Pirazinamid; Pirazinamida; Pirazinamide; Prazina; Pyrafat; Pyramide; Pyrazide; Pyrazinamdie; Pyrazinamidum; Pyrazineamide; Pyrazinecarboxamide; Rozide; Tebrazid; Tebrazio; Tisamid; Unipyranamide; Zinamide; Zinastat; P ezetamid; Pirazinamide [DCIT]; Pyrazine carboxamide; Pyrazine carboxylamide; Pyrazinecarboxylic acid amide; Pyrazinoic acid am ide; Pyrazinoic acid amide; DRG 0124; MK 56; P 7136; Pyrazinamide BP 2000; T 165; AZT + Pyrazinamide combination; D-50; Pirazinamida [INN-Spanish]; Pms-Pyrazinamide; Pyrazinamide (TN); Pyrazinamidum [INN-Latin]; D-50 (VAN); Pyrazinamide [INN:BAN:JAN]; Pyrazine-2-carboxamide; Pyrazinamide (JP15/USP/INN); Pyrazinoic acid amide, Pezetamid, Pyrafat, Zinamide, Tebrazid, Pyrafat, Pyrazinamide; 2-Carbamylpyrazine; 2-carbamyl pyrazine
Indication
Disease Entry ICD 11 Status REF
Mycobacterium infection 1B10-1B21 Approved [1], [2], [3]
Therapeutic Class
Antitubercular Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 123.11
Topological Polar Surface Area (xlogp) -0.6
Rotatable Bond Count (rotbonds) 1
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [4]
Bioavailability
90% of drug becomes completely available to its intended biological destination(s) [5]
Elimination
1.6% of drug is excreted from urine in the unchanged form [4]
Half-life
The concentration or amount of drug in body reduced by one-half in 9 - 10 hours [6]
Metabolism
The drug is metabolized via the hepatic [7]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 243.67441 micromolar/kg/day [8]
Water Solubility
The ability of drug to dissolve in water is measured as 15 mg/mL [4]
Chemical Identifiers
Formula
C5H5N3O
IUPAC Name
pyrazine-2-carboxamide
Canonical SMILES
C1=CN=C(C=N1)C(=O)N
InChI
InChI=1S/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9)
InChIKey
IPEHBUMCGVEMRF-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
1046
ChEBI ID
CHEBI:45285
CAS Number
98-96-4
DrugBank ID
DB00339
TTD ID
D0XF8W
INTEDE ID
DR1372
ACDINA ID
D00570

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Bacterial Fatty acid synthetase I (Bact inhA) TTVTX4N INHA_MYCTU Inhibitor [9]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [10]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [10]
Nicotinamidase (pncA) DERQS6E B0VA03_ACIBY Substrate [11]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Pyrazinamide (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Remdesivir DMBFZ6L Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Remdesivir. 1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019] [36]
Thioguanine DM7NKEV Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Thioguanine. Acute myeloid leukaemia [2A60] [37]
Bedaquiline DM3906J Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Bedaquiline. Antimicrobial drug resistance [MG50-MG52] [38]
Pexidartinib DMS2J0Z Major Increased risk of hepatotoxicity by the combination of Pyrazinamide and Pexidartinib. Bone/articular cartilage neoplasm [2F7B] [39]
Cannabidiol DM0659E Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Cannabidiol. Epileptic encephalopathy [8A62] [40]
Sulfinpyrazone DMEV954 Moderate Antagonize the effect of Pyrazinamide when combined with Sulfinpyrazone. Gout [FA25] [41]
Rifampin DMA8J1G Major Increased risk of hepatotoxicity by the combination of Pyrazinamide and Rifampin. HIV-infected patients with tuberculosis [1B10-1B14] [42]
Brentuximab vedotin DMWLC57 Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Brentuximab vedotin. Hodgkin lymphoma [2B30] [43]
Efavirenz DMC0GSJ Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Efavirenz. Human immunodeficiency virus disease [1C60-1C62] [44]
Mipomersen DMGSRN1 Major Increased risk of hepatotoxicity by the combination of Pyrazinamide and Mipomersen. Hyper-lipoproteinaemia [5C80] [45]
Teriflunomide DMQ2FKJ Major Increased risk of hepatotoxicity by the combination of Pyrazinamide and Teriflunomide. Hyper-lipoproteinaemia [5C80] [46]
BMS-201038 DMQTAGO Major Increased risk of hepatotoxicity by the combination of Pyrazinamide and BMS-201038. Hyper-lipoproteinaemia [5C80] [47]
Probenecid DMMFWOJ Moderate Antagonize the effect of Pyrazinamide when combined with Probenecid. Inborn purine/pyrimidine/nucleotide metabolism error [5C55] [41]
Methotrexate DM2TEOL Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Methotrexate. Leukaemia [2A60-2B33] [40]
Porfimer Sodium DM7ZWNY Moderate Increased risk of photosensitivity reactions by the combination of Pyrazinamide and Porfimer Sodium. Lung cancer [2C25] [48]
Calaspargase pegol DMQZBXI Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Calaspargase pegol. Malignant haematopoietic neoplasm [2B33] [49]
Idelalisib DM602WT Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Idelalisib. Mature B-cell leukaemia [2A82] [50]
Clofarabine DMCVJ86 Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Clofarabine. Mature B-cell lymphoma [2A85] [51]
Leflunomide DMR8ONJ Major Increased risk of hepatotoxicity by the combination of Pyrazinamide and Leflunomide. Rheumatoid arthritis [FA20] [46]
Trabectedin DMG3Y89 Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Trabectedin. Solid tumour/cancer [2A00-2F9Z] [40]
Epirubicin DMPDW6T Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Epirubicin. Solid tumour/cancer [2A00-2F9Z] [36]
Naltrexone DMUL45H Moderate Increased risk of hepatotoxicity by the combination of Pyrazinamide and Naltrexone. Substance abuse [6C40] [52]
⏷ Show the Full List of 22 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Stearic acid E00079 5281 Emulsifying agent; Solubilizing agent; Viscosity-controlling agent; lubricant
Brushite E00392 104805 Diluent
Carmellose sodium E00625 Not Available Disintegrant
Magnesium stearate E00208 11177 lubricant
Silicon dioxide E00670 Not Available Anticaking agent; Opacifying agent; Viscosity-controlling agent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Pyrazinamide 500 mg tablet 500 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

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: 7287).
2 Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 BDDCS applied to over 900 drugs
5 Critical Evaluation of Human Oral Bioavailability for Pharmaceutical Drugs by Using Various Cheminformatics Approaches
6 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
7 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.
8 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
9 Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis. Nat Med. 2000 Sep;6(9):1043-7.
10 The metabolism of pyrazoloacridine (NSC 366140) by cytochromes p450 and flavin monooxygenase in human liver microsomes. Clin Cancer Res. 2004 Feb 15;10(4):1471-80.
11 Specificity and mechanism of Acinetobacter baumanii nicotinamidase: implications for activation of the front-line tuberculosis drug pyrazinamide. Angew Chem Int Ed Engl. 2009;48(48):9176-9.
12 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
13 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
14 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
15 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
16 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
17 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
18 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
19 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
20 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
21 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.
22 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.
23 Endoxifen and other metabolites of tamoxifen inhibit human hydroxysteroid sulfotransferase 2A1 (hSULT2A1). Drug Metab Dispos. 2014 Nov;42(11):1843-50.
24 Cytochrome P450 1A2 (CYP1A2) activity and risk factors for breast cancer: a cross-sectional study. Breast Cancer Res. 2004;6(4):R352-65.
25 PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses. Pharmacogenet Genomics. 2015 Aug;25(8):416-26.
26 The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184.
27 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.
28 Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1993 Sep;348(3):332-7.
29 Metabolism and metabolic inhibition of xanthotoxol in human liver microsomes. Evid Based Complement Alternat Med. 2016;2016:5416509.
30 Diversity in enoyl-acyl carrier protein reductases. Cell Mol Life Sci. 2009 May;66(9):1507-17.
31 Mechanism of thioamide drug action against tuberculosis and leprosy. J Exp Med. 2007 Jan 22;204(1):73-8.
32 Affinium Pharmaceuticals Announces the Initiation of a Phase 1 Intravenous Clinical Trial of a New Antibiotic Prodrug, and the Closing of a Follow-on Financing Round. PR Newswire Sep. 4, 2013 10:16 PM.
33 SAR and pharmacophore models for the rhodanine inhibitors of Plasmodium falciparum enoyl-acyl carrier protein reductase. IUBMB Life. 2010 Mar;62(3):204-13.
34 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
35 2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections. Bioorg Med Chem. 2010 Nov 1;18(21):7475-85.
36 Cerner Multum, Inc. "Australian Product Information.".
37 Product Information. Aubagio (teriflunomide). Genzyme Corporation, Cambridge, MA.
38 Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
39 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
40 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
41 Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
42 Kunimoto D, Warman A, Beckon A, Doering D, Melenka L "Severe hepatotoxicity associated with rifampin-pyrazinamide preventative therapy requiring transplantation in an individual at low risk for hepatotoxicity." Clin Infect Dis 36 (2003): E158-61. [PMID: 12802781]
43 Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
44 Elsharkawy AM, Schwab U, McCarron B, et al. "Efavirenz induced acute liver failure requiring liver transplantation in a slow drug metaboliser." J Clin Virol 58 (2013): 331-3. [PMID: 23763943]
45 Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
46 Canadian Pharmacists Association.
47 Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
48 Blakely KM, Drucker AM, Rosen CF "Drug-induced photosensitivity-an update: Culprit drugs, prevention and management." Drug Saf 42 (2019): 827-47. [PMID: 30888626]
49 Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
50 Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
51 Product Information. Clolar (clofarabine). sanofi-aventis, Bridgewater, NJ.
52 Product Information. ReVia (naltrexone). DuPont Pharmaceuticals, Wilmington, DE.