DT-Web

DB00218 - Moxifloxacin


Identification
Name Moxifloxacin
Accession Number DB00218 (APRD00281)
Type small molecule
Description Moxifloxacin is a synthetic fluoroquinolone antibiotic agent. Bayer AG developed the drug (initially called BAY 12-8039) and it is marketed worldwide (as the hydrochloride) under the brand name Avelox (in some countries also Avalox) for oral treatment.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 401.4314
Groups approved
Monoisotopic Weight 401.175084476
Pharmacology
Indication For the treatment of sinus and lung infections such as sinusitis, pneumonia, and secondary infections in chronic bronchitis. Also for the treatment of bacterial conjunctivitis (pinkeye).
Mechanism of action The bactericidal action of moxifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division.
Absorption Well absorbed from the gastrointestinal tract. Absolute oral bioavailability is approximately 90%. Food has little effect on absorption.
Protein binding 50% bound to serum proteins, independent of drug concentration.
Biotransformation Approximately 52% or oral or intravenous dose is metabolized via glucuronide and sulphate conjugation. The cytochrome P450 system is not involved in metabolism. The sulphate conjugate accounts for 38% of the dose, and the glucuronide conjugate accounts for 14% of the dose.
Route of elimination Approximately 45% of an oral or intravenous dose of moxifloxacin is excreted as unchanged drug (~20% in urine and ~25% in feces).
Toxicity Symptoms of overdose include CNS and gastrointestinal effects such as decreased activity, somnolence, tremor, convulsions, vomiting, and diarrhea. The minimal lethal intravenous dose in mice and rats is 100 mg/kg.
Affected organisms
  • Enteric bacteria and other eubacteria
Interactions
Drug Interactions
Drug Mechanism of interaction
Acenocoumarol The quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of acenocoumarol.
Aluminium Formation of non-absorbable complexes
Amiodarone Increased risk of cardiotoxicity and arrhythmias
Anisindione The quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of anisindione.
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Bepridil Increased risk of cardiotoxicity and arrhythmias
Bretylium Increased risk of cardiotoxicity and arrhythmias
Calcium Formation of non-absorbable complexes
Dicumarol The quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of dicumarol.
Dihydroquinidine barbiturate Increased risk of cardiotoxicity and arrhythmias
Disopyramide Increased risk of cardiotoxicity and arrhythmias
Erythromycin Increased risk of cardiotoxicity and arrhythmias
Iron Formation of non-absorbable complexes
Iron Dextran Formation of non-absorbable complexes
Josamycin Increased risk of cardiotoxicity and arrhythmias
Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Magnesium Formation of non-absorbable complexes
Magnesium oxide Formation of non-absorbable complexes
Quinidine Increased risk of cardiotoxicity and arrhythmias
Quinidine barbiturate Increased risk of cardiotoxicity and arrhythmias
Quinupristin This combination presents an increased risk of toxicity
Sotalol Increased risk of cardiotoxicity and arrhythmias
Sucralfate Formation of non-absorbable complexes
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Tizanidine Moxifloxacin may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Warfarin The quinolone antibiotic, moxifloxacin, may increase the anticoagulant effect of warfarin.
Zinc Formation of non-absorbable complexes
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food Interactions
  • Take without regard to meals. Drink liberally. Absorption is not affected by lipid-rich meals or yogourt.

Targets


DNA topoisomerase 4 subunit A
Name DNA topoisomerase 4 subunit A
Gene Name parC
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Schafer J, Hovde LB, Simonson D, Rotschafer JC: In vitro pharmacodynamics of moxifloxacin versus levofloxacin against 4 strains of Streptococcus pneumoniae: 1 wild type, 2 first-step parC mutants, and 1 pump mutant. Diagn Microbiol Infect Dis. 2007 Oct 1;. - Pubmed
  • Deryke CA, Du X, Nicolau DP: Evaluation of bacterial kill when modelling the bronchopulmonary pharmacokinetic profile of moxifloxacin and levofloxacin against parC-containing isolates of Streptococcus pneumoniae. J Antimicrob Chemother. 2006 Sep;58(3):601-9. Epub 2006 Jul 19. - Pubmed
  • Perez-Vazquez M, Roman F, Aracil B, Canton R, Campos J: Laboratory detection of Haemophilus influenzae with decreased susceptibility to nalidixic acid, ciprofloxacin, levofloxacin, and moxifloxacin due to GyrA and ParC mutations. J Clin Microbiol. 2004 Mar;42(3):1185-91. - Pubmed
DTHybrid score 0.8862
DNA gyrase subunit A
Name DNA gyrase subunit A
Gene Name gyrA
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. - Pubmed
  • Schmitz FJ, Hofmann B, Hansen B, Scheuring S, Luckefahr M, Klootwijk M, Verhoef J, Fluit A, Heinz HP, Kohrer K, Jones ME: Relationship between ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin (BAY 12-8039) MICs and mutations in grlA, grlB, gyrA and gyrB in 116 unrelated clinical isolates of Staphylococcus aureus. J Antimicrob Chemother. 1998 Apr;41(4):481-4. - Pubmed
  • Brisse S, Milatovic D, Fluit AC, Verhoef J, Martin N, Scheuring S, Kohrer K, Schmitz FJ: Comparative in vitro activities of ciprofloxacin, clinafloxacin, gatifloxacin, levofloxacin, moxifloxacin, and trovafloxacin against Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, and Enterobacter aerogenes clinical isolates with alterations in GyrA and ParC proteins. Antimicrob Agents Chemother. 1999 Aug;43(8):2051-5. - Pubmed
  • Dridi L, Tankovic J, Burghoffer B, Barbut F, Petit JC: gyrA and gyrB mutations are implicated in cross-resistance to Ciprofloxacin and moxifloxacin in Clostridium difficile. Antimicrob Agents Chemother. 2002 Nov;46(11):3418-21. - Pubmed
DTHybrid score 0.9215
DNA topoisomerase 2-alpha
Name DNA topoisomerase 2-alpha
Gene Name TOP2A
Pharmacological action unknown
Actions inhibitor
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • Reuveni D, Halperin D, Shalit I, Priel E, Fabian I: Moxifloxacin enhances etoposide-induced cytotoxic, apoptotic and anti-topoisomerase II effects in a human colon carcinoma cell line. Int J Oncol. 2010 Aug;37(2):463-71. - Pubmed
  • Wohlkonig A, Chan PF, Fosberry AP, Homes P, Huang J, Kranz M, Leydon VR, Miles TJ, Pearson ND, Perera RL, Shillings AJ, Gwynn MN, Bax BD: Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance. Nat Struct Mol Biol. 2010 Sep;17(9):1152-3. Epub 2010 Aug 29. - Pubmed
DTHybrid score 0.7064

Predictions


Id Partner name Gene Name Score
6224 DNA gyrase subunit A gyrA 0.9215
886 DNA topoisomerase 4 subunit A parC 0.8862
6226 DNA topoisomerase 4 subunit A parC 0.8862
4200 Cytochrome P450 1A2 CYP1A2 0.1722
118 Organic cation/carnitine transporter 2 SLC22A5 0.0949
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0802
1729 Solute carrier family 22 member 6 SLC22A6 0.0761
1588 Multidrug resistance protein 1 ABCB1 0.0703
862 Multidrug resistance-associated protein 1 ABCC1 0.0614
4512 Cytochrome P450 3A4 CYP3A4 0.0549
4192 DNA topoisomerase 2-beta TOP2B 0.044
833 Organic cation/carnitine transporter 1 SLC22A4 0.0392
4118 Cytochrome P450 3A5 CYP3A5 0.0346
4180 DNA-(apurinic or apyrimidinic site) lyase APEX1 0.0305
6144 Solute carrier family 22 member 2 SLC22A2 0.0305
6107 Cytochrome P450 3A7 CYP3A7 0.0282
1353 DNA topoisomerase 1 TOP1 0.0202
3552 DNA topoisomerase 1 topA 0.0202
588 Chromodomain-helicase-DNA-binding protein 1 CHD1 0.0192
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0189
6137 Multidrug resistance-associated protein 6 ABCC6 0.0163
4119 Cytochrome P450 2D6 CYP2D6 0.015
6024 Cytochrome P450 1A1 CYP1A1 0.0147
5718 Cytochrome P450 2A6 CYP2A6 0.0132
2539 Tubulin alpha-1 chain TUBA4A 0.0126
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.012
161 Tubulin beta chain TUBB 0.0117
312 Tubulin beta chain TUB2 0.0117
723 Cytosolic phospholipase A2 PLA2G4A 0.0114
4757 Cytochrome P450 2C9 CYP2C9 0.0112
1898 Cytochrome P450 1B1 CYP1B1 0.0105
6016 Cytochrome P450 2C19 CYP2C19 0.0103
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0089
6148 Multidrug resistance-associated protein 7 ABCC10 0.0075
6013 Cytochrome P450 2E1 CYP2E1 0.0065
992 Protein tyrosine kinase 2 beta PTK2B 0.0064
4120 NADPH--cytochrome P450 reductase POR 0.0053
3947 Xanthine dehydrogenase/oxidase XDH 0.0045
6228 Nuclear receptor coactivator 1 NCOA1 0.0044
6241 Nuclear receptor coactivator 2 NCOA2 0.0043
869 Estrogen receptor beta ESR2 0.0041
776 Bile salt export pump ABCB11 0.0041
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.004
373 Transthyretin TTR 0.0038
6172 ATP-binding cassette sub-family B member 8, mitochondrial ABCB8 0.0036
136 Estrogen receptor ESR1 0.0035
908 Glutathione S-transferase theta-1 GSTT1 0.0032
337 NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial NDUFS7 0.0029
214 NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial NDUFS3 0.0029
803 NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial NDUFS2 0.0029
6168 Solute carrier family 22 member 16 SLC22A16 0.0029
6861 Alcohol dehydrogenase [NADP+] AKR1A1 0.0026
904 Glutathione S-transferase P GSTP1 0.0025
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0023
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0022
650 Aldo-keto reductase family 1 member C3 AKR1C3 0.0021
290 Prostaglandin G/H synthase 2 PTGS2 0.002
20 Prostaglandin G/H synthase 1 PTGS1 0.0019
2157 NAD(P)H dehydrogenase [quinone] 1 NQO1 0.0019
76 Nitric-oxide synthase, brain NOS1 0.0018
4924 Cytochrome P450 2C8 CYP2C8 0.0016
7 Nitric oxide synthase, inducible NOS2 0.0016
291 Nitric-oxide synthase, endothelial NOS3 0.0015
6030 Cytochrome P450 2B6 CYP2B6 0.0012
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