Absorption, Distribution and Excretion
Rapidly absorbed from the gastrointestinal tract. The absolute bioavailability averages approximately 71%.
Gemifloxacin and its metabolites are excreted via dual routes of excretion.Following oral administration of gemifloxacin to healthy subjects, a mean (± SD) of 61 ± 9.5% of the dose was excreted in the feces and 36 ± 9.3% in the urine as unchanged drug and metabolites. The mean (± SD) renal clearance following repeat doses of 320 mg was approximately 11.6 ± 3.9 L/hr (range 4.6-6 L/hr), which indicates active secretion is involved in the renal excretion of gemifloxacin.
1.66 to 12.12 L/kg
renal cl=11.6+/- 3.9 L/hr [Healthy subjects receiving repeat doses of 320 mg orally]
Gemifloxacin, given as an oral tablet, is rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations of gemifloxacin were observed between 0.5 and 2 hours following oral tablet administration and the absolute bioavailability of the 320 mg tablet averaged approximately 71% (95% CI 60%-84%). Following repeat oral doses of 320 mg to healthy subjects, the mean + or - SD maximal gemifloxacin plasma concentrations (Cmax) and systemic drug exposure (AUC (0-24)) were 1.61 + or - 0.51 ug/mL (range 0.70-2.62 ug/mL) and 9.93 + or - 3.07 ug.hr/mL (range 4.71-20.1 ug.hr/mL), respectively. In patients with respiratory and urinary tract infections (n=1423), similar estimates of systemic drug exposure were determined using a population pharmacokinetics analysis (geometric mean AUC (0-24), 8.36 ug.hr/mL; range 3.2 -47.7 ug.hr/mL).
In vitro binding of gemifloxacin to plasma proteins in healthy subjects is approximately 60 to 70% and is concentration independent. After repeated doses, the in vivo plasma protein binding in healthy elderly and young subjects ranged from 55% to 73% and was unaffected by age. Renal impairment does not significantly affect the protein binding of gemifloxacin. The blood-to-plasma concentration ratio of gemifloxacin was 1.2:1. The geometric mean for Vdss/F is 4.18 L/kg (range, 1.66 - 12.12 L/kg). Gemifloxacin is widely distributed throughout the body after oral administration. Concentrations of gemifloxacin in bronchoalveolar lavage fluid exceed those in the plasma. Gemifloxacin penetrates well into lung tissue and fluids.
Gemifloxacin and its metabolites are excreted via dual routes of excretion. Following oral administration of gemifloxacin to healthy subjects, a mean (+ or - SD) of 61 + or - 9.5% of the dose was excreted in the feces and 36 + or - 9.3% in the urine as unchanged drug and metabolites. The mean (+ or - SD) renal clearance following repeat doses of 320 mg was approximately 11.6 + or - 3.9 L/hr (range 4.6-17.6 L/hr), which indicates active secretion is involved in the renal excretion of gemifloxacin. The mean (+ or - SD) plasma elimination half-life at steady state following 320 mg to healthy subjects was approximately 7 + or - 2 hours (range 4-12 hours).

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Metabolism / Metabolites
Gemifloxacin is metabolized to a limited extent by the liver. All metabolites formed are minor (<10% of the administered oral dose); the principal ones are N-acetyl gemifloxacin, the E-isomer of gemifloxacin and the carbamyl glucuronide of gemifloxacin.
Gemifloxacin is metabolized to a limited extent by the liver. The unchanged compound is the predominant drug-related component detected in plasma (approximately 65%) up to 4 hours after dosing. All metabolites formed are minor (<10% of the administered oral dose); the principal ones are N-acetyl gemifloxacin, the E-isomer of gemifloxacin and the carbamyl glucuronide of gemifloxacin. Cytochrome P450 enzymes do not play an important role in gemifloxacin metabolism, and the metabolic activity of these enzymes is not significantly inhibited by gemifloxacin.

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Biological Half-Life
7 (± 2) hours
Gemifloxacin has an elimination half life of about 7 hours.

Hepatotoxicity
Gemifloxacin (jem" i flox' a sin), like other fluoroquinolones, is associated with a low rate (1% to 7%) of serum enzyme elevations during therapy, although this rate may be slightly higher than occurs with placebo or comparative agents. These abnormalities are generally mild, asymptomatic and transient, resolving even with continuation of therapy. Too few cases of hepatotoxicity due to gemifloxacin have been reported to provide a reliable description of its clinical features and course. However, the liver injury due to the fluoroquinolones appears to be a class effect, and gemifloxacin injury appears to share these characteristics. It is a far less common cause of liver injury than ciprofloxacin, levofloxacin or moxifloxacin, but cases have been reported. In general, fluoroquinone hepatotoxicity is marked by a short time to onset (a few days to 3 weeks); often presenting abruptly with marked nausea, fatigue, abdominal pain and jaundice. The pattern of serum enzyme elevations can be either hepatocellular or cholestatic, and cases with the shorter times to onset are usually more hepatocellular with markedly elevated ALT levels, and occasionally, with rapid worsening of prothrombin time and signs of hepatic failure. The onset of illness may occur a few days after the medication is stopped. Many (but not all) cases have had allergic manifestations with fever, rash and eosinophilia. Autoantibodies are usually not present.
Likelihood score: D (possible rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Gemifloxacin is not marketed in the United States. No information is available on the clinical use of gemifloxacin during breastfeeding; however, amounts in breastmilk appear to be low. 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 gemifloxacin is acceptable in nursing mothers. However, it is preferable to use an alternate drug for which safety information is available.
◉ 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.

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Protein Binding
60-70%

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Interactions
Possible pharmacologic interaction /with warfarin/ (increased prothrombin time (PT), international normalized ratio (INR), and/or bleeding). Consider that infectious disease and its accompanying inflammatory process, age, and general status of the patient also are risk factors for increased anticoagulation activity. Closely monitor PT, INR, or other suitable coagulation test.
Pharmacokinetic interaction (decreased absorption of gemifloxacin). Gemifloxacin should be taken at least 2 hours before sucralfate.
Pharmacokinetic interaction /with probenecid/ (decreased clearance of gemifloxacin).
Pharmacokinetic interaction (decreased absorption of gemifloxacin). Dietary supplements containing metal cations such as zinc, magnesium, or iron (e.g., multivitamins, ferrous sulfate) should be taken at least 3 hours before or 2 hours after gemifloxacin.
For more Interactions (Complete) data for Gemifloxacin (11 total), please visit the HSDB record page.

:Antimicrob Agents Chemother. 2003 Jan;47(1):440-1.;Antimicrob Agents Chemother. 1999 Sep;43(9):2231-5.

Therapeutic Uses
Anti-Bacterial Agents
Gemifloxacin is used for the treatment of acute bacterial exacerbation of chronic bronchitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae, H. parainfluenzae, or Moraxella catarrhalis. /Included in US product label/
Gemifloxacin is used for the treatment of community-acquired pneumonia (CAP) of mild to moderate severity caused by susceptible S. pneumoniae (including multidrug-resistant strains), H. influenzae, M. catarrhalis, Mycoplasma pneumoniae, Chlamydophila pneumoniae (formerly Chlamydia pneumoniae), or Klebsiella pneumoniae. /Included in US product label/

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Drug Warnings
/BOXED WARNING/ WARNING: Fluoroquinolones, including Factive, 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 and lung transplants.
/BOXED WARNING/ WARNING: Fluoroquinolones, including Factive, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid Factive in patients with known history of myasthenia gravis
Fluoroquinolones, including gemifloxacin, cause arthropathy and osteochondrosis in immature animals of various species. The relevance of these adverse effects in immature animals to use in humans is unknown.
Fluoroquinolones, including gemifloxacin, are associated with increased risk of tendinitis and tendon rupture in all age groups. This risk is further increased in older adults (usually those older than 60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients. Other factors that may independently increase risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones who did not have any of these risk factors. Fluoroquinolone-associated tendinitis and tendon rupture most frequently involve the Achilles tendon and may require surgical repair. Tendinitis and tendon rupture in the rotator cuff (shoulder), hand, biceps, thumb, and other tendon sites also reported. Tendon rupture can occur during or following fluoroquinolone therapy and has been reported up to several months after completion of therapy. Advise patients to rest and refrain from exercise and contact a clinician at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon or weakness or inability to use a joint). Discontinue gemifloxacin if pain, swelling, inflammation, or rupture of a tendon occurs.
For more Drug Warnings (Complete) data for Gemifloxacin (21 total), please visit the HSDB record page.

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Pharmacodynamics
Gemifloxacin is a quinolone/fluoroquinolone antibiotic. Gemifloxacin 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. Gemifloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria.

C18H20FN5O4

389.38

389.149

175463-14-6

Gemifloxacin mesylate;210353-53-0

9571107

Off-white, amorphous solid from chloroform-ethanol

1.6±0.1 g/cm3

638.9±65.0 °C at 760 mmHg

235-237°

340.2±34.3 °C

0.0±2.0 mmHg at 25°C

1.735

0.38

2

10

5

28

725

0

CO/N=C/1\CN(CC1CN)C2=C(C=C3C(=O)C(=CN(C3=N2)C4CC4)C(=O)O)F

ZRCVYEYHRGVLOC-HYARGMPZSA-N

InChI=1S/C18H20FN5O4/c1-28-22-14-8-23(6-9(14)5-20)17-13(19)4-11-15(25)12(18(26)27)7-24(10-2-3-10)16(11)21-17/h4,7,9-10H,2-3,5-6,8,20H2,1H3,(H,26,27)/b22-14+

7-[(4Z)-3-(aminomethyl)-4-methoxyiminopyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid

SB-265805 LB20304 SB265805Factive LB-20304SB 265805 Gemifloxacin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)