Ozenoxacin

Identification

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Name
Ozenoxacin
Accession Number
DB12924
Type
Small Molecule
Groups
Approved, Investigational
Description

To date, ozenoxacin has been used in trials studying the treatment of impetigo.

As of December 11, 2017 the FDA approved Ferrer Internacional S.A.'s Xepi (ozenoxacin 1%) as a topically applied cream indicated for the treatment of impetigo caused by Staphylococccus aureus or Streptococcus pyogenes in adult and pediatric patients 2 months of age and older.

Despite being a common and highly contagious bacerial skin infection that affects millions of children and adults in the United States each year, ozenoxacin cream is a novel, non-fluorinated quinolone that has demonstrated safe and effective therapy in both the adult and pediatric population.

Structure
Thumb
Synonyms
  • Ozenoxacin
  • Ozenoxacino
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
OzanexCream1 %TopicalFerrer Internacional S.A.2018-01-04Not applicableCanada
XepiCream10 mg/1gTopicalCutanea Life Sciences, Inc.2018-10-05Not applicableUs
XepiCream10 mg/1gTopicalMedimetriks Pharmaceuticals2017-12-152018-07-05Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories
UNII
V0LH498RFO
CAS number
245765-41-7
Weight
Average: 363.417
Monoisotopic: 363.158291548
Chemical Formula
C21H21N3O3
InChI Key
XPIJWUTXQAGSLK-UHFFFAOYSA-N
InChI
InChI=1S/C21H21N3O3/c1-11-8-13(9-23-20(11)22-3)15-6-7-16-18(12(15)2)24(14-4-5-14)10-17(19(16)25)21(26)27/h6-10,14H,4-5H2,1-3H3,(H,22,23)(H,26,27)
IUPAC Name
1-cyclopropyl-8-methyl-7-[5-methyl-6-(methylamino)pyridin-3-yl]-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
SMILES
CNC1=NC=C(C=C1C)C1=CC=C2C(=O)C(=CN(C3CC3)C2=C1C)C(O)=O

Pharmacology

Indication

Ozenoxacin cream is indicated for the topical treatment of impetigo caused by Staphylococcus aureus or Streptococcus pyogenes in patients aged 2 months of age and older Label.

Associated Conditions
Pharmacodynamics

Although the exposure response relationship for ozenoxacin after it has been applied topically has not yet been studied, a formal relationship is unlikely because systemic exposure of ozenoxacin following its topical application has been measured to be negligible 1.

Mechanism of action

Ozenoxacin is a quinolone antibiotic drug. And, like most quinolones, ozenoxacin predominately executes its mechanism of action by entering into bacterial cells and acting to inhibit the bacterial DNA replication enzymes DNA gyrase A and topoisomerase IV Label.

As DNA gyrase A and topoisomerase IV are essential to bacterial DNA replication activities including supercoiling, supercoil relaxation, chromosomal condensation, chromosomal decatenation 2 and more, their inhibition is the principal action of ozenoxacin's mechanism and it has been demonstrated to be bactericidal against S. aureus and S. pyogenes organisms Label.

TargetActionsOrganism
ADNA gyrase subunit A
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
ADNA topoisomerase 4 subunit A
inhibitor
Escherichia coli (strain K12)
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Four studies were performed in which varying strengths of ozenoxacin cream, up to 2% (twice the concentration of the marketed formulation), were administered to 110 patients. Three of the studies examined systemic absorption in healthy subjects and in subjects having impetigo. The studies were performed with either single or repeated application of up to 1 g ozenoxacin cream to intact or abraded skin (up to 200 cm squared surface area). No systemic absorption was seen in 84 of 86 subjects, and negligible systemic absorption was seen at the level of detection (0.489 ng/mL) in 2 subjects Label,1.

Volume of distribution

Ozenoxacin undergoes negligible systemic absorption after its topical administration Label. Subsequently, since negligible systemic absorption of ozenoxacin was observed in clinical studies, tissue distribution has not been investigated in humans either Label.

Protein binding

The plasma protein binding of [14 C]-ozenoxacin is moderate at ~80-85% and does not appear to be dependent on concentration Label.

Metabolism

Studies have demonstrated that ozenoxacin is not metabolized in the presence of fresh human skin discs and is minimally metabolized in human hepatocytes Label.

Route of elimination

Studies regarding elimination and excretion have not yet been investigated in humans due to the negligible systemic absorption observed in clinical studies Label.

Half life
Not Available
Clearance

Ozenoxacin undergoes negligible systemic absorption after its topical administration Label.

Toxicity

Ozenoxacin cream has the potential to cause rosacea and seborrheic dermatitis when administered topically on a patient. In clinical trials, only one adult patient treated with ozenoxacin cream reported such adverse reactions Label.

Much like other topical antibiotics, the prolonged use of ozenoxacin cream can result in the overgrowth of nonsusceptible bacteria and fungi. If such overgrowths develop into infections during therapy, discontinue use of the ozenoxacin cream and institue appropriate therapy for the infections Label.

Although clinical studies demonstrate negligible systemic absorption after topical administration of ozenoxacin, there are no formal available data on the use of ozenoxacin in pregnant women to inform any professional drug associated risk for use in pregnancy Label.

Although breastfeeding is not expected to result in exposure of the child to ozenoxacin owing to the negligible systemic absorption of ozenoxacin in humans following topical administration, no formal data are available regarding the presence of ozenoxacin in human milk and the effects of ozenoxacin on breasfed infants or on milk production Label.

Clinical experience with ozenoxacin cream has not identified differences in responses between elderly and younger patients Label.

The safety and effectiveness of ozenoxacin cream in pediatric patients 2 months and older is similar to that of adults, but the safety and effectiveness of ozenoxacin in pediatric patients younger than 2 months of age has not been formally establlished Label.

Long-term studies in animals to evaluate carcinogenic potential have not been conducted with ozenoxacin Label.

Ozenoxacin demonstrated no genotoxicity when evaluated in vitro for gene mutation and/or chromosomal effects in the Ames test, mouse lymphoma cell assay, or when evaluated in vivo in a rat micronucleus test with demonstrated systemic exposure Label.

Oral doses of ozenoxacin did not affect mating and fertility in male and female rats treated up to 500 mg/kg/day (about 8500 and 16,000 times respectively, the maximum human plasma concentration seen with dermal application of ozenoxacin 1% cream) Label.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Gropper S, Albareda N, Santos B, Febbraro S: Systemic bioavailability, safety and tolerability of topical ozenoxacin in healthy adult volunteers. Future Microbiol. 2014;9(8 Suppl):S11-6. doi: 10.2217/fmb.14.82. [PubMed:25209519]
  2. Fabrega A, Madurga S, Giralt E, Vila J: Mechanism of action of and resistance to quinolones. Microb Biotechnol. 2009 Jan;2(1):40-61. doi: 10.1111/j.1751-7915.2008.00063.x. Epub 2008 Oct 13. [PubMed:21261881]
External Links
PubChem Compound
9863827
PubChem Substance
347829069
ChemSpider
8039521
ChEBI
136050
ChEMBL
CHEMBL3990047
Wikipedia
Ozenoxacin
ATC Codes
D06AX14 — Ozenoxacin
AHFS Codes
  • 84:04.04 — Antibiotics
FDA label
Download (308 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentImpetigo2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CreamTopical1 %
CreamTopical10 mg/1g
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9180200No2015-11-102032-01-29Us
US9399014No2016-07-262029-12-15Us
US6335447No2002-01-012019-04-06Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.103 mg/mLALOGPS
logP2.76ALOGPS
logP2.54ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)6.1ChemAxon
pKa (Strongest Basic)6.77ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area82.53 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity106.11 m3·mol-1ChemAxon
Polarizability39.71 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as quinoline carboxylic acids. These are quinolines in which the quinoline ring system is substituted by a carboxyl group at one or more positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Quinoline carboxylic acids
Direct Parent
Quinoline carboxylic acids
Alternative Parents
Hydroquinolones / Hydroquinolines / Pyridinecarboxylic acids / Methylpyridines / Aminopyridines and derivatives / Imidolactams / Benzenoids / Vinylogous amides / Heteroaromatic compounds / Carboxylic acids
show 5 more
Substituents
Quinoline-3-carboxylic acid / Dihydroquinolone / Dihydroquinoline / Pyridine carboxylic acid / Pyridine carboxylic acid or derivatives / Aminopyridine / Methylpyridine / Pyridine / Benzenoid / Imidolactam
show 13 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function
DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, inc...
Gene Name
gyrA
Uniprot ID
P43700
Uniprot Name
DNA gyrase subunit A
Molecular Weight
97817.145 Da
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific Function
Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule. MukB stimulates th...
Gene Name
parC
Uniprot ID
P0AFI2
Uniprot Name
DNA topoisomerase 4 subunit A
Molecular Weight
83830.455 Da

Drug created on October 20, 2016 19:20 / Updated on June 26, 2019 06:06