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Moxifloxacin (Avelox, Avalox, Avelon, Vigamox, Moxeza; BAY12-8039; BAY12-8039; BAY 12-8039) is an orally bioactive, broad spectrum and 4th generation antibiotic agent of the fluoroquinolone class with high activity against both Gram positive and Gram negative bacteria. It acts as an inhibitor of DNA topoisomerase II and topoisomerase IV.
Physicochemical Properties
| Molecular Formula | C21H24FN3O4 |
| Molecular Weight | 401.43 |
| Exact Mass | 401.18 |
| Elemental Analysis | C, 62.83; H, 6.03; F, 4.73; N, 10.47; O, 15.94 |
| CAS # | 151096-09-2 |
| Related CAS # | Moxifloxacin Hydrochloride;186826-86-8;(Rac)-Moxifloxacin;354812-41-2;Moxifloxacin-d4;2596386-23-9;Moxifloxacin-d3 hydrochloride;2734919-98-1;Moxifloxacin-d3-1 hydrochloride;1246816-75-0;Moxifloxacin-13C,d3 hydrochloride;rac cis-Moxifloxacin-d4 hydrochloride;1217802-65-7 |
| PubChem CID | 152946 |
| Appearance | White to yellow solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 636.4±55.0 °C at 760 mmHg |
| Melting Point | 193-195 °C(lit.) |
| Flash Point | 338.7±31.5 °C |
| Vapour Pressure | 0.0±2.0 mmHg at 25°C |
| Index of Refraction | 1.633 |
| LogP | 1.6 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 29 |
| Complexity | 727 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | Cl[H].FC1C([H])=C2C(C(C(=O)O[H])=C([H])N(C2=C(C=1N1C([H])([H])[C@]2([H])[C@@]([H])(C([H])([H])C([H])([H])C([H])([H])N2[H])C1([H])[H])OC([H])([H])[H])C1([H])C([H])([H])C1([H])[H])=O |
| InChi Key | FABPRXSRWADJSP-MEDUHNTESA-N |
| InChi Code | InChI=1S/C21H24FN3O4/c1-29-20-17-13(19(26)14(21(27)28)9-25(17)12-4-5-12)7-15(22)18(20)24-8-11-3-2-6-23-16(11)10-24/h7,9,11-12,16,23H,2-6,8,10H2,1H3,(H,27,28)/t11-,16+/m0/s1 |
| Chemical Name | 1-Cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-((4aS,7aS)-octahydro-6H-pyrrolo(3,4-b)pyridin-6-yl)-4-oxo-3-quinolinecarboxylic acid |
| Synonyms | Avelox;Avalox;Avelon;Vigamox;Moxeza;BAY12-8039;BAY12-8039;BAY 12-8039 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Quinolone |
| ln Vitro | The time-kill curve and inhibition of intracellular growth experiments are used to compare the in vitro activities of loxifloxacin and amoxicillin using a model of L. monocytogenes EGDe-infected mouse macrophages derived from bone marrow. Much more quickly, doxifloxacin starts to work in the first three hours of incubation and completely sterilizes the broth in the final twenty-four hours. Many of the cells are still alive after a 24-hour incubation period, suggesting that doxifloxacin may have a protective effect against macrophage lysis[3]. |
| ln Vivo | Longer survival is associated with doxifloxacin (12 mg/kg; intravenous injection; once-three times daily; for 7 days; white male Wistar rats). Thirty hours after the bacterial challenge, tissue cultures reveal significantly less bacterial overgrowth in the lungs and spleens of moxifloxacin-treated animals than in saline-treated animals, and without any toxic effects[4]. |
| Cell Assay |
Bacterial strains.[2] Antimicrobial susceptibility to moxifloxacin was determined for a representative selection of the collection strains from the French National Reference Centre for Listeria. The strains studied included Listeria type strains and L. monocytogenes serovar reference strains (n = 16) (see Table S1 in the supplemental material), L. monocytogenes strains isolated from humans in 2005 (n = 205), a set of randomly selected L. monocytogenes strains isolated from food and the environment in 2005 (n = 183), and L. monocytogenes strains resistant to ciprofloxacin isolated from humans since 2000 (n = 8). Susceptibility testing.[2] The MICs of moxifloxacin and ciprofloxacin were determined by the Etest procedure (AB Biodisk, Solna, Sweden), according to the guidelines of the Antibiogram Committee of the French Society for Microbiology. To the best of our knowledge, there are no interpretative criteria for moxifloxacin and L. monocytogenes from any breakpoint committee. The isolates were categorized as susceptible, intermediate, or resistant according to the following breakpoints: 1 μg/ml ≤ MIC > 2 μg/ml. Time-kill curves.[2] The in vitro bactericidal activities of moxifloxacin and moxifloxacin were determined against a virulent strain of L. monocytogenes (strain EGDe) (11). Five milliliters of Mueller-Hinton (MH) broth was inoculated with 5 × 108 bacteria, and the mixture was incubated at 37°C. Moxifloxacin and amoxicillin were added to the MH broth suspension at various concentrations: 1× MIC, 4× MIC, 8× MIC, or 400× MIC. The last two concentrations correspond to the maximum serum concentration (Cmax) after the administration of clinically relevant doses of moxifloxacin and amoxicillin to humans, respectively. Bacterial counts were determined in triplicate at the indicated times of incubation with antibiotics by subculturing 10 μl of serial 10-fold dilutions of the MH broth suspension on brain heart infusion agar plates and on BHI agar supplemented with 2 μg/ml of moxifloxacin and incubation for 48 h. The results were expressed as the number of CFU per milliliter and corresponded to the means ± standard errors from three experiments. Bactericidal activity was defined as the killing of more than 99.9% of the initial inoculum after 24 h of incubation (i.e., a ≥3-log10 CFU/ml decrease in viable counts). The killing rate was defined as the decrease in the initial inoculum within the first 3 h. |
| Animal Protocol |
Animal Model: Stenotrophomonas maltophilia infected 144 white male Wistar rats, weighing 300–400 g and maturing between 18 and 22 weeks[4]. Dosage: 12 mg/kg Administration: Intravenous injection; once per day, twice per day, three times per day; for 7 days Result: demonstrated a marked reduction in the overgrowth of bacteria in the lungs and spleens without being toxic. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Well absorbed from the gastrointestinal tract. Absolute oral bioavailability is approximately 90%. Food has little effect on absorption. Approximately 45% of an oral or intravenous dose of moxifloxacin is excreted as unchanged drug (~20% in urine and ~25% in feces). 1.7 to 2.7 L/kg 12 +/- 2 L/hr Moxifloxacin is approximately 30-50% bound to serum proteins, independent of drug concentration. The volume of distribution of moxifloxacin ranges from 1.7 to 2.7 L/kg. Moxifloxacin is widely distributed throughout the body, with tissue concentrations often exceeding plasma concentrations. Moxifloxacin has been detected in the saliva, nasal and bronchial secretions, mucosa of the sinuses, skin blister fluid, subcutaneous tissue, skeletal muscle, and abdominal tissues and fluids following oral or intravenous administration of 400 mg. Approximately 45% of an oral or intravenous dose of moxifloxacin is excreted as unchanged drug (~20% in urine and ~25% in feces). A total of 96% + or - 4% of an oral dose is excreted as either unchanged drug or known metabolites. The mean (+ or - SD) apparent total body clearance and renal clearance are 12 + or - 2 L/hr and 2.6 + or - 0.5 L/hr, respectively. Moxifloxacin, given as an oral tablet, is well absorbed from the gastrointestinal tract. The absolute bioavailability of moxifloxacin is approximately 90 percent. Co-administration with a high fat meal (that is, 500 calories from fat) does not affect the absorption of moxifloxacin. The ocular penetration and pharmacokinetics of moxifloxacin in comparison to other fluoroquinolones (ofloxacin, ciprofloxacin, gatifloxacin, norfloxacin, levofloxacin, and lomefloxacin) have been determined by in vitro and ex vivo techniques, as well as in animal and human studies. ... The results consistently demonstrate higher maximum concentrations for moxifloxacin relative to the other fluoroquinolones in ocular tissues with levels well above its minimum inhibitory concentrations for relevant ocular pathogens. This superior performance is due to the unique structure of moxifloxacin that combines high lipophilicity for enhanced corneal penetration with high aqueous solubility at physiological pH. The latter property creates a high concentration gradient at the tear film/corneal epithelial interface providing a driving force for better ocular penetration for moxifloxacin. In addition, the higher concentration of moxifloxacin in VIGAMOX (i.e., 0.5% vs. 0.3%) allows more antibiotic to be available to ocular tissues. It is clear from the array of studies summarized in this report that moxifloxacin penetrates ocular tissues better (two- to three-fold) than gatifloxacin, ciprofloxacin, ofloxacin, or levofloxacin. This consistent, enhanced penetration of topical moxifloxacin offers powerful advantages for ophthalmic therapy. For more Absorption, Distribution and Excretion (Complete) data for Moxifloxacin (6 total), please visit the HSDB record page. Metabolism / Metabolites 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. Approximately 52% of an oral or intravenous dose of moxifloxacin is metabolized via glucuronide and sulfate conjugation. The cytochrome P450 system is not involved in moxifloxacin metabolism, and is not affected by moxifloxacin. The sulfate conjugate (M1) accounts for approximately 38% of the dose, and is eliminated primarily in the feces. Approximately 14% of an oral or intravenous dose is converted to a glucuronide conjugate (M2), which is excreted exclusively in the urine. Peak plasma concentrations of M2 are approximately 40% those of the parent drug, while plasma concentrations of M1 are generally less than 10% those of moxifloxacin. Biological Half-Life 11.5-15.6 hours (single dose, oral) The mean (+ or - SD) elimination half-life from plasma is 12 + or - 1.3 hours |
| Toxicity/Toxicokinetics |
Hepatotoxicity Moxifloxacin, like other fluoroquinolones, is associated with a low rate (1% to 3%) of serum enzyme elevations during therapy. These abnormalities are generally mild, asymptomatic and transient, resolving even with continuation of therapy. Moxifloxacin has been linked to rare but occasionally severe and even fatal cases of acute liver injury. The time to onset is typically short (1 day to 3 weeks) and the presentation is often abrupt with nausea, fatigue, abdominal pain and jaundice. The pattern of serum enzyme elevations can be either hepatocellular or cholestatic, cases with the shorter times to onset usually being more hepatocellular. In addition, the onset of illness may occur a few days after the medication is stopped. Many (but not all) cases have prominent allergic manifestations with fever and rash, and the liver injury may occur in the context of a generalized hypersensitivity reaction (Case 1). Autoantibodies are usually not present. Cases with a cholestatic pattern of enzymes may run a prolonged course but are usually self-limiting, although at least one case of chronic cholestasis and vanishing bile duct syndrome leading to liver failure has been published. Most reported cases have been mild with recovery within 4 to 8 weeks of onset. Likelihood score: B (rare but likely cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of moxifloxacin during breastfeeding. Fluoroquinolones have traditionally not been used in infants because of concern about adverse effects on the infants' developing joints. However, recent studies indicate little risk. The calcium in milk might prevent absorption of the small amounts of fluoroquinolones in milk, but insufficient data exist to prove or disprove this assertion. Use of moxifloxacin is acceptable in nursing mothers with monitoring of the infant for possible effects on the gastrointestinal flora, such as diarrhea or candidiasis (thrush, diaper rash). However, it is preferable to use an alternate drug for which safety information is available. Maternal use of an eye drop that contains moxifloxacin presents negligible risk for the nursing infant. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding 50% bound to serum proteins, independent of drug concentration. Interactions Fifteen males and 5 females, mean age of 34 years, were given moxifloxacin under two conditions separated by a minimum 7-day washout period: alone as a single oral 400 mg dose, and immediately following 10 mg of IM morphine sulfate. Moxifloxacin serum concentrations were determined by a validated HPLC procedure. Pharmacokinetic parameters including Cmax, Tmax, AUC0-infinity, and t1/2 were estimated using noncompartmental methods and analyzed using ANOVA. Results: Moxifloxacin pharmacokinetics were similar between the two treatments. Geometric least square mean Cmax, values for moxifloxacin were 3.4 mg (alone) vs 2.8 mg/L (with morphine) (90% confidence interval (CI) of moxifloxacin alone vs with morphine sulfate was 71%-98%). Corresponding geometric mean AUC0-infinity values were 41.5 and 39.6 mgh/L (90% CI = 87%-104%). Tmax and t1/2 values for moxifloxacin were similar when coadministered with morphine. Conclusion: Moxifloxacin was well tolerated when taken with and without morphine sulfate. Administration of a single IM dose of morphine did not reduce the bioavailability or alter the elimination profile of oral moxifloxacin. Implications: Concurrent administration of morphine and moxifloxacin is unlikely to reduce the efficacy of this quinolone. Pharmacokinetic interaction (decreased absorption of oral moxifloxacin). Moxifloxacin should be given at least 4 hours before or 8 hours after buffered didanosine (pediatric oral solution admixed with antacid). Concomitant use of corticosteroids increases the risk of severe tendon disorders (e.g., tendinitis, tendon rupture), especially in geriatric patients older than 60 years of age. Quinolones, including Avelox, have been reported to enhance the anticoagulant effects of warfarin or its derivatives in the patient population. In addition, infectious disease and its accompanying inflammatory process, age, and general status of the patient are risk factors for increased anticoagulant activity. Therefore the prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if a quinolone is administered concomitantly with warfarin or its derivatives. For more Interactions (Complete) data for Moxifloxacin (17 total), please visit the HSDB record page. |
| References |
[1]. Am J Health Syst Pharm, 2001. 58(5): p. 379-88. [2]. Antimicrob Agents Chemother. 2008 May;52(5):1697-702. [3]. Drugs. 2000 Jan;59(1):115-39. [4]. Microbiol Immunol. 2014 Feb;58(2):96-102. [5]. Tuberculosis (Edinb).2008 Mar;88(2):127-31 [6]. JPharmBiomedAnal.2005Jun1;38(1):8-13. |
| Additional Infomation |
Therapeutic Uses Anti-Infective Agents Moxifloxacin hydrochloride ophthalmic solution is used for the treatment of conjunctivitis caused by susceptible strains of Corynebacterium spp., Micrococcus luteus, Staphylococcus aureus, S. epidermidis, S. haemolyticus, S. hominis, S. warneri, Streptococcus pneumoniae, viridans streptococci, Acinetobacter lwoffii, Haemophilus influenzae, H. parainfluenzae, or Chlamydia trachomatis. /Included in US product label/ Moxifloxacin is used for the treatment of acute bacterial sinusitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis; acute bacterial exacerbations of chronic bronchitis caused by susceptible S. pneumoniae, H. influenzae, H. parainfluenzae, Klebsiella pneumoniae, Staphylococcus aureus (oxacillin-susceptible [methicillin-susceptible] strains), or M. catarrhalis; and community-acquired pneumonia (CAP) caused by susceptible S. pneumoniae (including multidrug-resistant strains), S. aureus (oxacillin-susceptible strains), K. pneumoniae, H. influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae (formerly Chlamydia pneumoniae), or M. catarrhalis. /Included in US product label/ Moxifloxacin is used for the treatment of uncomplicated skin and skin structure infections caused by susceptible S. aureus (oxacillin-susceptible strains) or Streptococcus pyogenes (group A beta-hemolytic streptococci) and for the treatment of complicated skin and skin structure infections caused by susceptible S. aureus (oxacillin-susceptible strains), Escherichia coli, K. pneumoniae, or Enterobacter cloacae. /Included in US product label/ For more Therapeutic Uses (Complete) data for Moxifloxacin (12 total), please visit the HSDB record page. Drug Warnings /BOXED WARNING/ WARNING: Fluoroquinolones, including Avelox, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. /BOXED WARNING/ WARNING: Fluoroquinolones, including Avelox, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid Avelox in patients with known history of myasthenia gravis. Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions reported in patients receiving fluoroquinolones, including moxifloxacin. Although generally reported after multiple doses, these reactions may occur with first dose. Some reactions have been accompanied by cardiovascular collapse, loss of consciousness, tingling, edema (pharyngeal or facial), dyspnea, urticaria, or pruritus. In addition, other possible severe and potentially fatal reactions (may be hypersensitivity reactions or of unknown etiology) have been reported, most frequently after multiple doses. These include fever, rash or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome), vasculitis, arthralgia, myalgia, serum sickness, allergic pneumonitis, interstitial nephritis, acute renal insufficiency or failure, hepatitis, jaundice, acute hepatic necrosis or failure, anemia (including hemolytic and aplastic), thrombocytopenia (including thrombotic thrombocytopenic purpura), leukopenia, agranulocytosis, pancytopenia, and/or other hematologic effects. Discontinue moxifloxacin at first appearance of rash, jaundice, or any other sign of hypersensitivity. Institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen). Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness have been reported with fluoroquinolones. For more Drug Warnings (Complete) data for Moxifloxacin (22 total), please visit the HSDB record page. Pharmacodynamics Moxifloxacin is a quinolone/fluoroquinolone antibiotic. Moxifloxacin can be used to treat infections caused by the following bacteria: Aerobic Gram-positive microorganisms: _Corynebacterium_ species, _Micrococcus luteus_, _Staphylococcus aureus_, _Staphylococcus epidermidis_, _Staphylococcus haemolyticus_, _Staphylococcus hominis_, _Staphylococcus warneri_, _Streptococcus pneumoniae_, and _Streptococcus viridans_ group. Aerobic Gram-negative microorganisms: _Acinetobacter lwoffii_, _Haemophilus influenzae_, and _Haemophilus parainfluenzae_. Other microorganisms: _Chlamydia trachomatis_. Moxifloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Moxifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~31.25 mg/mL (~77.85 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4911 mL | 12.4555 mL | 24.9109 mL | |
| 5 mM | 0.4982 mL | 2.4911 mL | 4.9822 mL | |
| 10 mM | 0.2491 mL | 1.2455 mL | 2.4911 mL |