Details of the Drug

General Information of Drug (ID: DMJFD2I)

Drug Name
ABT-492
Synonyms
Delafloxacin; 189279-58-1; ABT-492; WQ-3034; Abt 492; 1-(6-AMINO-3,5-DIFLUOROPYRIDIN-2-YL)-8-CHLORO-6-FLUORO-7-(3-HYDROXYAZETIDIN-1-YL)-4-OXO-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC ACID; ABT492; RX-3341; UNII-6315412YVF; 6315412YVF; 1-(6-amino-3,5-difluoro-2-pyridyl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-quinoline-3-carboxylic acid; 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxoquinoline-3-carboxylic acid; Delafloxacin [USAN:INN]; Delafloxacinum; Delafloxacin (USAN)
Indication
Disease Entry ICD 11 Status REF
Bacterial infection 1A00-1C4Z Phase 3 [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 440.8
Topological Polar Surface Area (xlogp) 2.7
Rotatable Bond Count (rotbonds) 3
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 11
ADMET Property
Bioavailability
The bioavailability of drug is 58.8% [2]
Clearance
The mean total clearance of drug is 16.3 L/h [3]
Elimination
After a single intravenous dose, 65% of Delafloxacin was excreted in the urine either unchanged or as glucuronide metabolites with 28% excreted unchanged in the feces [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 3.7 hours [2]
Metabolism
The drug is metabolized via the glucuronidation [2]
Unbound Fraction
The unbound fraction of drug in plasma is 0.16% [4]
Vd
The volume of distribution (Vd) of drug is 30-48 L [3]
Chemical Identifiers
Formula
C18H12ClF3N4O4
IUPAC Name
1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxoquinoline-3-carboxylic acid
Canonical SMILES
C1C(CN1C2=C(C=C3C(=C2Cl)N(C=C(C3=O)C(=O)O)C4=C(C=C(C(=N4)N)F)F)F)O
InChI
InChI=1S/C18H12ClF3N4O4/c19-12-13-7(1-9(20)14(12)25-3-6(27)4-25)15(28)8(18(29)30)5-26(13)17-11(22)2-10(21)16(23)24-17/h1-2,5-6,27H,3-4H2,(H2,23,24)(H,29,30)
InChIKey
DYDCPNMLZGFQTM-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
487101
CAS Number
189279-58-1
DrugBank ID
DB11943
TTD ID
D0V9BU
INTEDE ID
DR1895
ACDINA ID
D00175

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Staphylococcus Topoisomerase IV (Stap-coc parC) TTIXTO3 PARC_STAAS Modulator [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)
Main DME 		DEYGVN4 UD11_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from ABT-492 (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Gilteritinib DMWQ4MZ Moderate Decreased clearance of ABT-492 due to the transporter inhibition by Gilteritinib. Acute myeloid leukaemia [2A60] [22]
Ag-221 DMS0ZBI Moderate Decreased clearance of ABT-492 due to the transporter inhibition by Ag-221. BCR-ABL1-negative chronic myeloid leukaemia [2A41] [22]
Erdafitinib DMI782S Moderate Decreased clearance of ABT-492 due to the transporter inhibition by Erdafitinib. Bladder cancer [2C94] [23]
PF-04449913 DMSB068 Moderate Decreased clearance of ABT-492 due to the transporter inhibition by PF-04449913. Chronic myelomonocytic leukaemia [2A40] [24]
Lurbinectedin DMEFRTZ Minor Decreased absorption of ABT-492 due to intestinal mucosa variation caused by Lurbinectedin. Lung cancer [2C25] [25]
Rucaparib DM9PVX8 Moderate Decreased metabolism of ABT-492 caused by Rucaparib mediated inhibition of UGT. Ovarian cancer [2C73] [26]
Choline salicylate DM8P137 Moderate Additive CNS depression effects by the combination of ABT-492 and Choline salicylate. Postoperative inflammation [1A00-CA43] [27]
Darolutamide DMV7YFT Moderate Decreased clearance of ABT-492 due to the transporter inhibition by Darolutamide. Prostate cancer [2C82] [28]
Tedizolid DMG2SKR Moderate Decreased clearance of ABT-492 due to the transporter inhibition by Tedizolid. Skin and skin-structure infection [1F28-1G0Z] [24]
⏷ Show the Full List of 9 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Kyselina citronova E00014 311 Acidulant; Antioxidant; Buffering agent; Complexing agent; Flavoring agent
Meglumine E00181 8567 Buffering agent
Crospovidone E00626 Not Available Disintegrant
Edetate disodium E00186 8759 Complexing agent
Magnesium palmitostearate E00532 18763844 Other agent
Magnesium stearate E00208 11177 lubricant
Povidone E00667 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Sodium bicarbonate E00424 516892 Alkalizing agent; Diluent
Sodium dihydrogenorthophosphate E00559 23672064 Buffering agent; Complexing agent
Sodium phosphate monobasic monohydrate E00428 516949 Buffering agent; Complexing agent
Vinylpyrrolidone E00668 Not Available Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Water E00035 962 Solvent
Betadex sulfobutyl ether sodium E00589 66577045 Solubilizing agent
Cellulose microcrystalline E00698 Not Available Adsorbent; Suspending agent; Diluent
⏷ Show the Full List of 14 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Delafloxacin 450 mg tablet 450 mg Oral Tablet Oral
Delafloxacin Meglumine 300 mg For Injection 300 mg For Injection Intravenous
Delafloxacin Meglumine 450 mg tablet 450 mg Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

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4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Contrasting Effects of Acidic pH on the Extracellular and Intracellular Activities of the Anti-Gram-Positive Fluoroquinolones Moxifloxacin and Delafloxacin against Staphylococcus aureus
6 Delafloxacin: place in therapy and review of microbiologic, clinical and pharmacologic properties. Infect Dis Ther. 2018 Jun;7(2):197-217.
7 Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
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9 Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
10 UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
11 Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
12 Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
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14 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
15 Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
16 Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
17 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
18 In vitro and in vivo antibacterial activity of T-3912, a novel non-fluorinated topical quinolone. J Antimicrob Chemother. 2002 Mar;49(3):455-65.
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20 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
21 2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
22 Cerner Multum, Inc. "Australian Product Information.".
23 Product Information. Balversa (erdafitinib). Janssen Products, LP, Horsham, PA.
24 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
25 Johnson EJ, MacGowan AP, Potter MN, et al "Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy." J Antimicrob Chemother 25 (1990): 837-42. [PMID: 2373666]
26 EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring.".
27 Product Information. Factive (gemifloxacin). GeneSoft Inc, San Francisco, CA.
28 Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.