AVIBACTAM

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C7H11N3O6S
Molecular Weight	265.244
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=O)[C@@H]1CC[C@@H]2C[N@]1C(=O)N2OS(O)(=O)=O

InChI

InChIKey=NDCUAPJVLWFHHB-UHNVWZDZSA-N

InChI=1S/C7H11N3O6S/c8-6(11)5-2-1-4-3-9(5)7(12)10(4)16-17(13,14)15/h4-5H,1-3H2,(H2,8,11)(H,13,14,15)/t4-,5+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206494s002lbl.pdf | https://www.future-science.com/doi/full/10.4155/fmc-2016-0078 | https://www.ncbi.nlm.nih.gov/pubmed/22753474 | https://www.ncbi.nlm.nih.gov/pubmed/15254025 | https://www.ncbi.nlm.nih.gov/pubmed/23371303

Avibactam (formerly NXL104, AVE1330A) is a synthetic non-β-lactam, covalent, slowly reversible β-lactamase inhibitor that inhibits the activities of Ambler class A and C β-lactamases and some Ambler class D enzymes. The combination of ceftazidime with avibactam exhibited broad-spectrum activity against Ambler class A- and class C-producing Enterobacteriaceae. AVYCAZ is a combination of ceftazidime, a cephalosporin, and avibactam indicated for the treatment of patients with the following infections caused by designated susceptible microorganisms: Complicated Intra-abdominal Infections, used in combination with metronidazole and Complicated Urinary Tract Infections, including Pyelonephritis.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial beta-lactamase TEM 10 Target ID: CHEMBL2364670 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23371303	Inhibitor 8297		8.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Complicated Intra-abdominal Infections 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23371303 https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206494s002lbl.pdf	Curative		Approved 8429	AVYCAZ Approved Use AVYCAZ is a combination of ceftazidime, a cephalosporin, and avibactam, a beta-lactamase inhibitor, indicated for the treatment of patients 18 years or older with the following infections caused by designated susceptible microorganisms: complicated Intra-abdominal Infections (cIAI), used in combination with metronidazole and complicated Urinary Tract Infections (cUTI), including Pyelonephritis. Launch Date 2015
Complicated urinary tract infections 11 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23371303 https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/206494s002lbl.pdf	Curative		Approved 8429	AVYCAZ Approved Use AVYCAZ is a combination of ceftazidime, a cephalosporin, and avibactam, a beta-lactamase inhibitor, indicated for the treatment of patients 18 years or older with the following infections caused by designated susceptible microorganisms: complicated Intra-abdominal Infections (cIAI), used in combination with metronidazole and complicated Urinary Tract Infections (cUTI), including Pyelonephritis. Launch Date 2015

C_max

Value	Dose	Co-administered	Analyte	Population
14.6 mg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g 3 times / day multiple, intravenous dose: 0.5 g route of administration: Intravenous experiment type: MULTIPLE co-administered: CEFTAZIDIME	CEFTAZIDIME	AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
15.2 mg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g single, intravenous dose: 0.5 g route of administration: Intravenous experiment type: SINGLE co-administered: Ceftazidime	Ceftazidime	[NO STEREO] AVE-1330A FREE ACID\|[NO STEREO] AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
38.2 mg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g 3 times / day multiple, intravenous dose: 0.5 g route of administration: Intravenous experiment type: MULTIPLE co-administered: CEFTAZIDIME	CEFTAZIDIME	AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
42.1 mg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g single, intravenous dose: 0.5 g route of administration: Intravenous experiment type: SINGLE co-administered: Ceftazidime	Ceftazidime	[NO STEREO] AVE-1330A FREE ACID\|[NO STEREO] AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.71 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g 3 times / day multiple, intravenous dose: 0.5 g route of administration: Intravenous experiment type: MULTIPLE co-administered: CEFTAZIDIME	CEFTAZIDIME	AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.22 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g single, intravenous dose: 0.5 g route of administration: Intravenous experiment type: SINGLE co-administered: Ceftazidime	Ceftazidime	[NO STEREO] AVE-1330A FREE ACID\|[NO STEREO] AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
93% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/206494s005,s006lbl.pdf	0.5 g single, intravenous dose: 0.5 g route of administration: Intravenous experiment type: SINGLE co-administered: Ceftazidime	Ceftazidime	[NO STEREO] AVE-1330A FREE ACID\|[NO STEREO] AVIBACTAM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1000 mg 3 times / day multiple, intravenous Highest studied dose Dose: 1000 mg, 3 times / day Route: intravenous Route: multiple Dose: 1000 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25813217	healthy, 18–45 years n = 6 Health Status: healthy Age Group: 18–45 years Sex: M Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/25813217	Sources: https://pubmed.ncbi.nlm.nih.gov/25813217
2000 mg single, intravenous Highest studied dose Dose: 2000 mg Route: intravenous Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/25813217	healthy, 18–45 years n = 6 Health Status: healthy Age Group: 18–45 years Sex: M Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/25813217	Sources: https://pubmed.ncbi.nlm.nih.gov/25813217
500 mg single, oral Dose: 500 mg Route: oral Route: single Dose: 500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/25813217	healthy, 28.9 years n = 8 Health Status: healthy Age Group: 28.9 years Sex: M Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/25813217	Sources: https://pubmed.ncbi.nlm.nih.gov/25813217

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781	inhibitor 1767 inducer 389	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 402 MRP4 204 CYP 111 UGT1A1 204 P-gp 1461 BCRP 699 OAT1 599 OAT3 642 OATP1B1 788 OATP1B3 706 OCT1 512 OCT2 647 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882 CYP3A4/5 278	OAT1 326 OAT3 339 P-gp 1537 BCRP 561 MRP4 77 OCT2 355	CYP1A2 701 CYP2B6 547 CYP2E1 128

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP 147	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=38 Page: 38.0	no
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
MRP4 238	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	no
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=38 Page: 38.0	no
CYP2E1 970	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/206494s007lbl.pdf#page=21 Page: 21.0	yes

Drug as victim

Target	Modality	Activity
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=38 Page: 38.0	no
MRP4 77	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=38 Page: 38.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=38 Page: 38.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=38 Page: 38.0	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=4 Page: 4.0	yes
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000CllinPharmR.pdf#page=4 Page: 4.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/206494Orig1s000PharmR.pdf#page=18 Page: 18.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:85984	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:85984
ChemicalBook	CB02582836	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB02582836
ZINC	ZINC000009302239	http://zinc15.docking.org/substances/ZINC000009302239

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

AVYCAZ 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) for injection administered every 8 hours by intravenous (IV) infusion over 2 hours in patients 18 years of age and older with creatinine clearance (CrCl) greater than 50 mL/min. For treatment of Complicated Intra-abdominal Infections (cIAI), metronidazole should be given concurrently. Recommended duration of treatment: cIAI: 5 to 14 days, Complicated Urinary Tract Infections (cUTI) including pyelonephritis: 7 to 14 days.

Route of Administration: Intravenous

In Vitro Use Guide

MICs of ceftazidime/AVE1330A(avibactam) for Enterobacteriaceae were at least eight-fold lower than those of ceftazidime alone. All of the Escherichia coli, Klebsiella pneumoniae, Citrobacter and Proteus mirabilis strains, including ceftazidime-resistant isolates, were inhibited at 4-8 mg/L. Only 2 mg/L were required to inhibit other Proteeae, Enterobacter, Salmonella and Serratia.

Name

Type

Language

AVIBACTAM

Official Name

English

Avibactam [WHO-DD]

Common Name

English

(1R,2S,5R)-7-OXO-6-SULFOOXY-1,6-DIAZABICYCLO(3.2.1)OCTANE-2-CARBOXAMIDE

Common Name

English

ZAVICEFTA COMPONENT AVIBACTAM

Brand Name

English

SULFURIC ACID, MONO((1R,2S,5R)-2-(AMINOCARBONYL)-7-OXO-1,6-DIAZABICYCLO(3.2.1)OCT-6-YL) ESTER

Common Name

English

AVIBACTAM COMPONENT OF ZAVICEFTA

Brand Name

English

NXL-104 FREE ACID

Code

English

avibactam [INN]

Common Name

English

AVIBACTAM [USAN]

Common Name

English

AVIBACTAM [MI]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175930