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]
Endometritis	N.A.	Approved	[2]
Peritonitis	N.A.	Approved	[2]
Pseudomonas aeruginosa infectious disease	N.A.	Approved	[2]
Urinary tract infection	GC08	Approved	[2]
Pelvic inflammatory disease	GA05	Investigative	[2]

• Therapeutic Class: Antibiotics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 435.4
  Logarithm of the Partition Coefficient (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 [3]
  Clearance: The clearance of drug is 91 mL/min in healthy subjects []
  Elimination: 68% 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 1.7 hours [4]
  Metabolism: The drug is metabolized via the hydrolysis of the beta-lactam bond []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 305.44019 micromolar/kg/day [5]
  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 []
  Water Solubility: The ability of drug to dissolve in water is measured as 10 mg/mL [3]
• 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
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[7]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Substrate	[7]
Beta-lactamase (blaB)	DEP0IWS	A0A378EHS6_KLEPR	Substrate	[8]
Beta-lactamase (blaB)	DEEAL81	BLA2_KLEPO	Substrate	[9]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
HLA class II histocompatibility antigen, DP alpha 1 chain (HLA-DPA1)	OT7OG7Y2	DPA1_HUMAN	Gene/Protein Processing	[10]

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]	[11]
Mycophenolic acid	DMRBMAU	Moderate	Altered absorption of Aztreonam due to GI flora changes caused by Mycophenolic acid.	Crohn disease [DD70]	[12]
Warfarin	DMJYCVW	Moderate	Increased risk of bleeding by the combination of Aztreonam and Warfarin.	Supraventricular tachyarrhythmia [BC81]	[11]
Mycophenolate mofetil	DMPQAGE	Moderate	Altered absorption of Aztreonam due to GI flora changes caused by Mycophenolate mofetil.	Transplant rejection [NE84]	[12]

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] Aztreonam FDA Label
• [3] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] 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
• [6] 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.
• [7] Aztreonam decreases hepatic microsomal cytochrome P450 in cynomolgus monkeys. Pharmacology. 1994 Mar;48(3):137-42.
• [8] 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.
• [9] 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.
• [10] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [11] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [12] Product Information. CellCept (mycophenolate mofetil). Roche Laboratories, Nutley, NJ.