Details of the Drug

General Information of Drug (ID: DMDNJHG)

Drug Name
Aztreonam
Synonyms
Azactam; Primbactam; Azactam (TN); SQ-26776; Monobactam, SQ 26776, Squibb 26776, Aztreonam; [2S-[2alpha,3beta(Z)]]-2-[[[1-(2-Amino-4-thiazolyl)-2-[(2-methyl-4-oxo-1-sulfo-3-azetidinyl)amino]-2-oxoethylidene]amino]oxy]-2-methylpropanoic acid; 2-({[(1Z)-1-(2-amino-1,3-thiazol-4-yl)-2-{[(2S,3S)-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino}-2-oxoethylidene]amino}oxy)-2-methylpropanoic acid; 2-[(Z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(2S,3S)-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid
Indication
Disease Entry ICD 11 Status REF
Bacterial infection 1A00-1C4Z Approved [1]
Therapeutic Class
Antibiotics
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 435.4
Topological Polar Surface Area (xlogp) 0.3
Rotatable Bond Count (rotbonds) 7
Hydrogen Bond Donor Count (hbonddonor) 4
Hydrogen Bond Acceptor Count (hbondacc) 12
ADMET Property
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
Clearance
The clearance of drug is 91 mL/min in healthy subjects [3]
Elimination
68% of drug is excreted from urine in the unchanged form [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 1.7 hours [4]
Metabolism
The drug is metabolized via the hydrolysis of the beta-lactam bond [5]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 305.44019 micromolar/kg/day [6]
Unbound Fraction
The unbound fraction of drug in plasma is 0.4% [4]
Vd
The volume of distribution (Vd) of drug is 12.6 L [3]
Water Solubility
The ability of drug to dissolve in water is measured as 10 mg/mL [2]
Chemical Identifiers
Formula
C13H17N5O8S2
IUPAC Name
2-[(Z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(2S,3S)-2-methyl-4-oxo-1-sulfoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoic acid
Canonical SMILES
C[C@H]1[C@@H](C(=O)N1S(=O)(=O)O)NC(=O)/C(=N\\OC(C)(C)C(=O)O)/C2=CSC(=N2)N
InChI
InChI=1S/C13H17N5O8S2/c1-5-7(10(20)18(5)28(23,24)25)16-9(19)8(6-4-27-12(14)15-6)17-26-13(2,3)11(21)22/h4-5,7H,1-3H3,(H2,14,15)(H,16,19)(H,21,22)(H,23,24,25)/b17-8-/t5-,7-/m0/s1
InChIKey
WZPBZJONDBGPKJ-VEHQQRBSSA-N
Cross-matching ID
PubChem CID
5742832
ChEBI ID
CHEBI:161680
CAS Number
78110-38-0
DrugBank ID
DB00355
TTD ID
D0F2XV
INTEDE ID
DR0169
ACDINA ID
D00857

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Bacterial Penicillin binding protein 3 (Bact mrcA) TT85JMW FTSI_ECOLI Binder [7]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [8]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [8]
Cytochrome P450 3A7 (CYP3A7) DERD86B CP3A7_HUMAN Substrate [8]
Beta-lactamase (blaB) DEP0IWS A0A378EHS6_KLEPR Substrate [9]
Beta-lactamase (blaB) DEEAL81 BLA2_KLEPO Substrate [10]
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 Aztreonam (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Anisindione DM2C48U Moderate Increased risk of bleeding by the combination of Aztreonam and Anisindione. Coagulation defect [3B10] [43]
Mycophenolic acid DMU65NK Moderate Altered absorption of Aztreonam due to GI flora changes caused by Mycophenolic acid. Crohn disease [DD70] [44]
Warfarin DMJYCVW Moderate Increased risk of bleeding by the combination of Aztreonam and Warfarin. Supraventricular tachyarrhythmia [BC81] [43]
Mycophenolate mofetil DMPQAGE Moderate Altered absorption of Aztreonam due to GI flora changes caused by Mycophenolate mofetil. Transplant rejection [NE84] [44]

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

DIG
DIG Name DIG ID PubChem CID Functional Classification
Arginine E00112 6322 Buffering agent; Dispersing agent
Aminutrin E00087 5962 Buffering agent
Sodium chloride E00077 5234 Diluent; Tonicity agent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Aztreonam 75mg/vial for solution 75mg/vial For Solution Inhalation
Aztreonam 500mg/vial injectable 500mg/vial Injectable Injection
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
2 BDDCS applied to over 900 drugs
3 An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 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.
6 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
7 Penicillin-binding protein PBP2 of Escherichia coli localizes preferentially in the lateral wall and at mid-cell in comparison with the old cell pole. Mol Microbiol. 2003 Jan;47(2):539-47.
8 Aztreonam decreases hepatic microsomal cytochrome P450 in cynomolgus monkeys. Pharmacology. 1994 Mar;48(3):137-42.
9 Analysis of the drug-resistant characteristics of Klebsiella pneumoniae isolated from the respiratory tract and CTX-M ESBL genes. Genet Mol Res. 2015 Oct 5;14(4):12043-8.
10 Antibiotic resistance and production of extended-spectrum beta-lactamases amongst Klebsiella spp. from intensive care units in Europe. J Antimicrob Chemother. 1996 Sep;38(3):409-24.
11 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.
12 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
13 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.
14 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
15 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.
16 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.
17 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
18 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.
19 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.
20 Drug related genetic polymorphisms affecting adverse reactions to methotrexate, vinblastine, doxorubicin and cisplatin in patients with urothelial cancer. J Urol. 2008 Dec;180(6):2389-95.
21 Human prostate CYP3A5: identification of a unique 5'-untranslated sequence and characterization of purified recombinant protein. Biochem Biophys Res Commun. 1999 Jul 14;260(3):676-81.
22 Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett. 2005 Jan 10;217(1):61-72.
23 Drug Interactions Flockhart Table
24 Induction of hepatic CYP2E1 by a subtoxic dose of acetaminophen in rats: increase in dichloromethane metabolism and carboxyhemoglobin elevation. Drug Metab Dispos. 2007 Oct;35(10):1754-8.
25 Urinary 6 beta-hydroxycortisol excretion in rheumatoid arthritis. Br J Rheumatol. 1997 Jan;36(1):54-8.
26 Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94.
27 Kinetics and regulation of cytochrome P450-mediated etoposide metabolism. Drug Metab Dispos. 2004 Sep;32(9):993-1000.
28 Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos. 2005 May;33(5):664-71.
29 The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver. J Steroid Biochem Mol Biol. 1993 Jan;44(1):61-7.
30 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
31 Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. Drug Metab Dispos. 2004 Feb;32(2):259-66.
32 The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalyst. Drug Metab Dispos. 2013 Sep;41(9):1686-94.
33 Oral streptococcal strains isolated from odontogenic infections and their susceptibility to antibiotics. Rev Med Chir Soc Med Nat Iasi. 2006 Oct-Dec;110(4):1012-5.
34 Clinical relevance of antibiotic-induced endotoxin release in patients undergoing hepatic resection. World J Surg. 1999 Jan;23(1):75-9.
35 Genetic analyses of beta-lactamase negative ampicillin-resistant strains of Haemophilus influenzae isolated in Okinawa, Japan. Jpn J Infect Dis. 2006 Feb;59(1):36-41.
36 Bactericidal effect of piperacillin alone and combined. Presse Med. 1986 Dec 20;15(46):2297-302.
37 Moxalactam (6059-S), a new 1-oxa-beta-lactam: binding affinity for penicillin-binding proteins of Escherichia coli K-12.
38 In vitro evaluation of E1040, a new cephalosporin with potent antipseudomonal activity. Antimicrob Agents Chemother. 1988 May;32(5):693-701.
39 Association of amino acid substitutions in penicillin-binding protein 3 with beta-lactam resistance in beta-lactamase-negative ampicillin-resistant Haemophilus influenzae. Antimicrob Agents Chemother. 2001 Jun;45(6):1693-9.
40 Mode of Action of the Monobactam LYS228 and Mechanisms Decreasing In Vitro Susceptibility in Escherichia coli and Klebsiella pneumoniae. Antimicrob Agents Chemother. 2018 Sep 24;62(10):e01200-18.
41 DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
42 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
43 Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
44 Product Information. CellCept (mycophenolate mofetil). Roche Laboratories, Nutley, NJ.