AZTREONAM LYSINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C13H17N5O8S2.C6H14N2O2
Molecular Weight	581.62
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NCCCC[C@H](N)C(O)=O.C[C@H]1[C@H](NC(=O)C(=N/OC(C)(C)C(O)=O)\C2=CSC(N)=N2)C(=O)N1S(O)(=O)=O

InChI

InChIKey=KPPBAEVZLDHCOK-JHBYREIPSA-N

InChI=1S/C13H17N5O8S2.C6H14N2O2/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;7-4-2-1-3-5(8)6(9)10/h4-5,7H,1-3H3,(H2,14,15)(H,16,19)(H,21,22)(H,23,24,25);5H,1-4,7-8H2,(H,9,10)/b17-8-;/t5-,7-;5-/m00/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2244291
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050580s040,050632s013lbl.pdf https://www.ncbi.nlm.nih.gov/pubmed/27334663

Aztreonam is the first monocyclic beta-lactam antibiotic (monobactam) originally isolated from Chromobacterium violaceum. Aztreonam has a high affinity for the protein-binding protein 3 (PBP-3) of aerobic gram-negative bacteria. Most of these organisms are inhibited and killed at low concentrations of the drug. Aztreonam must be administered as an intravenous or intramuscular injection (AZACTAM®), or inhaled (CAYSTON®). Aztreonam for injection is indicated for the treatment of the following infections caused by susceptible gram-negative microorganisms: urinary tract, lower respiratory tract, skin and skin-structure, intra-abdominal and gynecologic infections as well as for septicemia. Aztreonam for inhalation solution is indicated to improve respiratory symptoms in cystic fibrosis patients with Pseudomonas aeruginosa.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial penicillin-binding protein 233 Target ID: CHEMBL2354204 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2244291	Inhibitor 8297		0.03 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Urinary tract infections 205 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2010/065439Orig1s000.pdf	Curative	Approved 8429	AZACTAM Approved Use Aztreonam for Injection is indicated for the treatment of infections caused by susceptible gram-negative microorganisms. Launch Date 1986
Lower respiratory tract infections 51 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2010/065439Orig1s000.pdf	Curative	Approved 8429	AZACTAM Approved Use Aztreonam for Injection is indicated for the treatment of infections caused by susceptible gram-negative microorganisms. Launch Date 1986
Sepsis 71 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2010/065439Orig1s000.pdf	Curative	Approved 8429	AZACTAM Approved Use Aztreonam for Injection is indicated for the treatment of infections caused by susceptible gram-negative microorganisms. Launch Date 1986
Skin and skin structure infections 80 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050580s040,050632s013lbl.pdf	Curative	Approved 8429	AZACTAM Approved Use Aztreonam for Injection is indicated for the treatment of infections caused by susceptible gram-negative microorganisms. Launch Date 1986
Intra-abdominal infections 49 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2010/065439Orig1s000.pdf	Curative	Approved 8429	AZACTAM Approved Use Aztreonam for Injection is indicated for the treatment of infections caused by susceptible gram-negative microorganisms. Launch Date 1986
Gynecologic infections 18 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/anda/2010/065439Orig1s000.pdf	Curative	Approved 8429	AZACTAM Approved Use Aztreonam for Injection is indicated for the treatment of infections caused by susceptible gram-negative microorganisms. Launch Date 1986
Respiratory symptoms in cystic fibrosis (CF) patients with Pseudomonas aeruginosa 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050814s007lbl.pdf	Palliative	Approved 8429	CAYSTON Approved Use CAYSTON® is indicated to improve respiratory symptoms in cystic fibrosis (CF) patients with Pseudomonas aeruginosa. Launch Date 2010

C_max

Value	Dose	Analyte	Population
204 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050580s040,050632s013lbl.pdf	2 g single, intravenous dose: 2 g route of administration: Intravenous experiment type: SINGLE co-administered:	AZTREONAM serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
54 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050580s040,050632s013lbl.pdf	500 mg single, intravenous dose: 500 mg route of administration: Intravenous experiment type: SINGLE co-administered:	AZTREONAM serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
90 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050580s040,050632s013lbl.pdf	1 g single, intravenous dose: 1 g route of administration: Intravenous experiment type: SINGLE co-administered:	AZTREONAM serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
208 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3710959	1 g 1 times / day steady-state, intravenous dose: 1 g route of administration: Intravenous experiment type: STEADY-STATE co-administered:		AZTREONAM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.67 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3710959	1 g 1 times / day steady-state, intravenous dose: 1 g route of administration: Intravenous experiment type: STEADY-STATE co-administered:		AZTREONAM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
44% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/050580s040,050632s013lbl.pdf	500 mg single, intravenous dose: 500 mg route of administration: Intravenous experiment type: SINGLE co-administered:		AZTREONAM serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
30 mg/kg single, intravenous Recommended Dose: 30 mg/kg Route: intravenous Route: single Dose: 30 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/3774385/	unhealthy, 10 - 18 years n = 10 Health Status: unhealthy Condition: cystic fibrosis Age Group: 10 - 18 years Sex: unknown Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/3774385/	Sources: https://pubmed.ncbi.nlm.nih.gov/3774385/
1 g single, intramuscular Recommended Dose: 1 g Route: intramuscular Route: single Dose: 1 g Sources: https://pubmed.ncbi.nlm.nih.gov/3102347/	unhealthy, 18 - 75 years n = 102 Health Status: unhealthy Condition: urogenital gonorrhoea Age Group: 18 - 75 years Sex: M+F Population Size: 102 Sources: https://pubmed.ncbi.nlm.nih.gov/3102347/	Sources: https://pubmed.ncbi.nlm.nih.gov/3102347/
1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 343 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 343 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	Other AEs: Pain, Erythema... Other AEs: Pain (12%) Erythema (2.9%) Induration (0.9%) Phlebitis (2.1%) Blood eosinophils increased (6.3%) Increased platelets (3.6%) Neutropenia (3.2%) AST increased (3.8%) ALT increased (6.5%) Increased serum creatinine (5.8%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 612 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	Other AEs: Rash, Diarrhea... Other AEs: Rash (4.3%) Diarrhea (1.4%) Fever (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf

AEs

AE	Significance	Dose	Population
Induration	0.9%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 343 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 343 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
Pain	12%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 343 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 343 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
Phlebitis	2.1%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 343 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 343 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
Erythema	2.9%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 343 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 343 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
Neutropenia	3.2%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 343 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 343 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
Increased platelets	3.6%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 343 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 343 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
AST increased	3.8%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 343 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 343 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
Increased serum creatinine	5.8%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 343 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 343 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
Blood eosinophils increased	6.3%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 343 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 343 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
ALT increased	6.5%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 343 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 343 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
Fever	1%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 612 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
Diarrhea	1.4%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 612 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf
Rash	4.3%	1 g 3 times / day steady, intramuscular (median) Recommended Dose: 1 g, 3 times / day Route: intramuscular Route: steady Dose: 1 g, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf	unhealthy, children n = 612 Health Status: unhealthy Condition: infections Age Group: children Sex: unknown Population Size: 612 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/050580s042lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 450 18	CYP 450 31	CYP 450 10

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 450 20	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/050814Orig1s000PharmR.pdf#page=3 Page: 3.0	unlikely
CYP 450 20	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/050814Orig1s000PharmR.pdf#page=3 Page: 3.0	unlikely

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 450 31	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/050814Orig1s000PharmR.pdf#page=3 Page: 3.0	no

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:161680	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:161680
ChemicalBook	CB0386184	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0386184
MolPort	MolPort-003-886-345	https://www.molport.com/shop/molecule-link/MolPort-003-886-345
Selleck Chemicals	Aztreonam(Azactam)	http://www.selleckchem.com/products/Aztreonam(Azactam).html
ZINC	ZINC000003830264	http://zinc15.docking.org/substances/ZINC000003830264
eMolecules	17497503	https://www.emolecules.com/cgi-bin/more?vid=17497503

PubMed

Title	Date	PubMed
Broth microdilution testing of susceptibilities to 30 antimicrobial agents of Mycobacterium avium strains from patients with acquired immune deficiency syndrome.	1987 Oct	3501698
In-vitro activity of seventeen antimicrobial compounds against seven species of mycobacteria.	1988 Dec	3243734
Contribution of beta-lactamases to beta-lactam susceptibilities of susceptible and multidrug-resistant Mycobacterium tuberculosis clinical isolates.	1998 Jun	9624510
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942

Patents

Sample Use Guides

In Vivo Use Guide

Urinary tract infections (adults): 0.5-1 g 2-3 times/day. Moderately severe systemic infections (adults): 1-2 g 2-3 times/day. Severe systemic or life-threatening infections (adults): 2 g 3-4 times/day. Maximum recommended dose for adults is 8 g per day. Mild to moderate infections (pediatric patients): 30 mg/kg 3 times/day Moderate to severe infections (pediatric patients): 30 mg/kg 3-4 times/day. Maximum recommended dose for pediatric patients is 120 mg/kg/day. Inhalation solution: one dose (one single use vial and one ampule of diluent) 3 times a day for 28 days.

Route of Administration: Other

In Vitro Use Guide

In vitro, minimum inhibition concentration (MIC) values against almost all of the Enterobacteriaceae, Neisseria and Haemophilus strains were below 1 microgram per milliliter. MIC values against Pseudomonas aeruginosa were about 8 ug/ml.

Name

Type

Language

AZTREONAM LYSINE

Official Name

English

L-LYSINE, MONO(2-(((Z)-(1-(2-AMINO-4-THIAZOLYL)-2-(((2S,3S)-2-METHYL-4-OXO-1-SULFO-3-AZETIDINYL)AMINO)-2-OXOETHYLIDENE)AMINO)OXY)-2-METHYLPROPANOATE)

Common Name

English

L-LYSINE, 2-(((Z)-(1-(2-AMINO-4-THIAZOLYL)-2-(((2S,3S)-2-METHYL-4-OXO-1-SULFO-3-AZETIDINYL)AMINO)-2-OXOETHYLIDENE)AMINO)OXY)-2-METHYLPROPANOATE (1:1)

Common Name

English

AZTREONAM L-LYSINE SALT [MI]

Common Name

English

AZTREONAM LYSINATE

Common Name

English

CORUS1020

Code

English

Aztreonam lysine [WHO-DD]

Common Name

English

AZTREONAM LYSINE [MART.]

Common Name

English

AZTREONAM L-LYSINE SALT

Common Name

English

AZTREONAM LYSINE [USAN]

Common Name

English

AZTREONAM LYSINE [EMA EPAR]

Common Name

English

CAYSTON

Brand Name

English

CORUS-1020

Code

English

L-LYSINE, MONO(2-(((Z)-(1-(2-AMINOTHIZOL-4-YL)-2-((2S,3S)-2-METHYL-4-OXO-1-SULFOAZETIDIN-3-YL)AMINO)-2-OXOETHYLIDENE)AMINO)OXY)-2-METHYLPROPANOATE

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/04/204