CEFTOLOZANE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H30N12O8S2
Molecular Weight	666.69
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12SCC(C[N+]3=CC(NC(=O)NCCN)=C(N)N3C)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC(C)(C)C(O)=O)\C4=NSC(N)=N4)C([O-])=O

InChI

InChIKey=JHFNIHVVXRKLEF-DCZLAGFPSA-N

InChI=1S/C23H30N12O8S2/c1-23(2,20(40)41)43-31-11(15-30-21(26)45-32-15)16(36)29-12-17(37)35-13(19(38)39)9(8-44-18(12)35)6-34-7-10(14(25)33(34)3)28-22(42)27-5-4-24/h7,12,18,25H,4-6,8,24H2,1-3H3,(H7,26,27,28,29,30,32,36,38,39,40,41,42)/b31-11-/t12-,18-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206829s001lbl.pdf
Curator's Comment: Description was created using several sources including: http://www.ncbi.nlm.nih.gov/pubmed/18701284; http://www.ncbi.nlm.nih.gov/pubmed/17145788; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264669/

Ceftolozane is a novel a cephalosporin-class antibacterial drug. In combination with a beta-lactamase inhibitor tazobactam (ZERBAXA, ceftolozane/tazobactam ) ceftolozane, is currently indicated for the treatment of the adult patients with complicated intra-abdominal infections caused by designated Gram-negative and Gram-positive microorganisms and complicated urinary tract infections caused by certain Gram-negative bacteria, including those caused by multi-drug resistant Pseudomonas aeruginosa. To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZERBAXA and other antibacterial drugs, ZERBAXA should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. Safety and effectiveness in pediatric patients have not been established.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial penicillin-binding protein 233 Target ID: CHEMBL2354204 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206829s001lbl.pdf	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Intra-abdominal infections 49 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206829s001lbl.pdf	Curative		Approved 8429	ZERBAXA Approved Use To treat adults with complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI) Launch Date 2014
Pyelonephritis 5 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206829s001lbl.pdf	Curative		Approved 8429	ZERBAXA Approved Use To treat adults with complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). Launch Date 2014

C_max

Value	Dose	Co-administered	Analyte	Population
69.1 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206829lbl.pdf	1 g single, intravenous dose: 1 g route of administration: Intravenous experiment type: SINGLE co-administered: TAZOBACTAM	TAZOBACTAM	CEFTOLOZANE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
74.4 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206829lbl.pdf	1 g 3 times / day steady-state, intravenous dose: 1 g route of administration: Intravenous experiment type: STEADY-STATE co-administered: TAZOBACTAM	TAZOBACTAM	CEFTOLOZANE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
172 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206829lbl.pdf	1 g single, intravenous dose: 1 g route of administration: Intravenous experiment type: SINGLE co-administered: TAZOBACTAM	TAZOBACTAM	CEFTOLOZANE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
182 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206829lbl.pdf	1 g 3 times / day steady-state, intravenous dose: 1 g route of administration: Intravenous experiment type: STEADY-STATE co-administered: TAZOBACTAM	TAZOBACTAM	CEFTOLOZANE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.77 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206829lbl.pdf	1 g single, intravenous dose: 1 g route of administration: Intravenous experiment type: SINGLE co-administered: TAZOBACTAM	TAZOBACTAM	CEFTOLOZANE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
3.12 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206829lbl.pdf	1 g 3 times / day steady-state, intravenous dose: 1 g route of administration: Intravenous experiment type: STEADY-STATE co-administered: TAZOBACTAM	TAZOBACTAM	CEFTOLOZANE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
81.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206829lbl.pdf	1 g single, intravenous dose: 1 g route of administration: Intravenous experiment type: SINGLE co-administered: TAZOBACTAM	TAZOBACTAM	CEFTOLOZANE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
81.5% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206829lbl.pdf	1 g 3 times / day steady-state, intravenous dose: 1 g route of administration: Intravenous experiment type: STEADY-STATE co-administered: TAZOBACTAM	TAZOBACTAM	CEFTOLOZANE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
2000 mg single, intravenous Highest studied dose Dose: 2000 mg Route: intravenous Route: single Dose: 2000 mg Sources: https://pubmed.ncbi.nlm.nih.gov/20457817	healthy, 29.5 years (range: 19–59 years) n = 6 Health Status: healthy Age Group: 29.5 years (range: 19–59 years) Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/20457817	Sources: https://pubmed.ncbi.nlm.nih.gov/20457817
1000 mg 3 times / day steady, intravenous Highest studied dose Dose: 1000 mg, 3 times / day Route: intravenous Route: steady Dose: 1000 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20457817	healthy, 33.0 years (range: 22–55 years) n = 6 Health Status: healthy Age Group: 33.0 years (range: 22–55 years) Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/20457817	Other AEs: Flushing... Other AEs: Flushing (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/20457817
1500 mg 2 times / day steady, intravenous Highest studied dose Dose: 1500 mg, 2 times / day Route: intravenous Route: steady Dose: 1500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20457817	healthy, 33.0 years (range: 22–55 years) n = 6 Health Status: healthy Age Group: 33.0 years (range: 22–55 years) Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/20457817	Sources: https://pubmed.ncbi.nlm.nih.gov/20457817

AEs

AE	Significance	Dose	Population
Flushing	1 patient	1000 mg 3 times / day steady, intravenous Highest studied dose Dose: 1000 mg, 3 times / day Route: intravenous Route: steady Dose: 1000 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20457817	healthy, 33.0 years (range: 22–55 years) n = 6 Health Status: healthy Age Group: 33.0 years (range: 22–55 years) Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/20457817

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
supressor 21	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B6 810 CYP2C8 911 CYP2C19 1478 OAT1 599 OAT3 642 OCT1 512 OCT2 647 OATP1B1 788 OATP1B3 706 P-gp 1461 BCRP 699 BSEP 402 MRP2 383 MATE1 306 MATE2 263	P-gp 1537 BCRP 561	CYP 76

Drug as perpetrator

Target	Modality	Activity
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
CYP 147	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP1A2 1692	supressor 155 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	no
MRP2 475	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	no
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	weak [IC50 >3754 uM]
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	weak [IC50 >3754 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	weak [IC50 >3754 uM]
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=52 Page: 52.0	weak [IC50 >3754 uM]
CYP3A4 1925	supressor 155 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=51 Page: 51.0	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=136 Page: 136.0	no
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000ClinPharmR.pdf#page=136 Page: 136.0	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206829Orig1s000PharmR.pdf#page=42 Page: 42.0

Sourcing

Vendor/Aggregator	ID	URL
Alsachim	4958	http://www.alsachim.com/product-C6347-glo.bal-view.html
BOC Sciences	689293-68-3	https://www.bocsci.com/ceftolozane-cas-689293-68-3-item-476118.html
BioChemPartner	BCP23708	http://www.biochempartner.com/689293-68-3-BCP23708
ChemShuttle	139011	http://www.chemshuttle.com/catalogsearch/result/?q=689293-68-3&cat=
Chemieliva Pharmaceutical Co., Ltd	PBCM0767804
Clearsynth	CS-CX-00213	https://www.clearsynth.com/en/CSCX00213.html
Compound Cloud	49863420
Compound Cloud	52918380
Compound Cloud	53234134
Google Patents	10725219	https://patents.google.com/?q=JHFNIHVVXRKLEF-VWDPFFEDSA-N
MuseChem	I005927
MuseChem	I005928
ShangHai Biochempartner	BCP23708
Smolecule	S523133	http://www.smolecule.com/products/s523133
THE BioTek	bt-263493	https://www.thebiotek.com/product/inhibitors/bt-263493
ZINC	ZINC000009164421	http://zinc15.docking.org/substances/ZINC000009164421
ZINC	ZINC001850018719	http://zinc15.docking.org/substances/ZINC001850018719
ZINC	ZINC001850018720	http://zinc15.docking.org/substances/ZINC001850018720
ZINC	ZINC001850018721	http://zinc15.docking.org/substances/ZINC001850018721
ZINC	ZINC001850018722	http://zinc15.docking.org/substances/ZINC001850018722

PubMed

Title	Date	PubMed
Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis.	2010 Feb	20050849
Ceftolozane/Tazobactam: a new option in the treatment of complicated gram-negative infections.	2014 Dec	25516692
Ceftolozane/tazobactam: a novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli.	2014 Jan	24352909

Patents

Sample Use Guides

In Vivo Use Guide

1.5 gram (g) (ceftolozane 1 g and tazobactam 0.5 g) for injection, every 8 hours by intravenous infusion administered over 1 hour for patients 18 years or older with creatinine clearance (CrCl) greater than 50 mL/min

Route of Administration: Intravenous

In Vitro Use Guide

Minimum inhibitory concentrations (MIC) were obtained for ceftolozane and tazobactam in the susceptibility testing using fixed 4 ug/mL concentration of tazobactam and less then 8 ug/mL for susceptible bacteria

Name

Type

Language

CEFTOLOZANE

Official Name

English

CXA-101 FREE BASE

Code

English

CEFTOLOZANE [MI]

Common Name

English

Ceftolozane [WHO-DD]

Common Name

English

(6R,7R)-3-((5-AMINO-4-(((2-AMINOETHYL)CARBAMOYL)AMINO)-1-METHYL-1H-PYRAZOL-2-IUM-2-YL)METHYL)-7-((2Z)-2-(5-AMINO-1,2,4-THIADIAZOL-3-YL)-2-(((2-CARBOXYPROPAN-2-YL)OXY)IMINO)ACETAMIDO)-8-OXO-5-THIA-1-AZABICYCLO(4.2.0)OCT-2-ENE-2-CARBOXYLATE

Common Name

English

CEFTOLOZANE [USAN]

Common Name

English

ceftolozane [INN]

Common Name

English

CEFTOLOZANE [VANDF]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175488