Absorption, Distribution and Excretion
Gemifloxacin is rapidly absorbed from the gastrointestinal tract. The absolute bioavailability is approximately 71% on average.
Gemifloxacin and its metabolites are excreted via two routes. In healthy subjects, after oral administration of gemimifloxacin, a mean (± standard deviation) 61 ± 9.5% of the dose was excreted unchanged in feces and 36 ± 9.3% in urine. After repeated administration of 320 mg, the mean (± standard deviation) renal clearance was approximately 11.6 ± 3.9 L/hr (range 4.6–6 L/hr), indicating that renal excretion of gemimifloxacin involves active secretion.
1.66 to 12.12 L/kg
Renal clearance = 11.6 ± 3.9 L/hr [Repeated oral administration of 320 mg in healthy subjects]
Oral tablets of gemimifloxacin are rapidly absorbed from the gastrointestinal tract. Peak plasma concentrations of gemifloxacin were observed between 0.5 and 2 hours after oral administration of the tablets, with an absolute bioavailability of approximately 71% (95% CI 60%–84%) for the 320 mg tablet. In healthy subjects, after repeated oral administration of 320 mg gemifloxacin, the mean ± standard deviation of the maximum plasma concentration (Cmax) and systemic drug exposure (AUC(0–24)) were 1.61 ± 0.51 μg/mL (range 0.70–2.62 μg/mL) and 9.93 ± 3.07 μg·hr/mL (range 4.71–20.1 μg·hr/mL), respectively. Similar estimates of systemic drug exposure were determined using population pharmacokinetic analysis in patients with respiratory and urinary tract infections (n=1423) (geometric mean AUC(0–24) 8.36 μg·hr/mL; range 3.2–47.7 μg·hr/mL).
Gemifloxacin exhibits approximately 60% to 70% in vitro binding to plasma proteins in healthy subjects, regardless of concentration. Following multiple administrations, plasma protein binding in healthy elderly and young subjects ranges from 55% to 73%, unaffected by age. Renal impairment has no significant effect on the protein binding of gemifloxacin. The plasma-to-dose ratio of gemifloxacin is 1.2:1. The geometric mean of Vdss/F is 4.18 L/kg (range: 1.66–12.12 L/kg). After oral administration, gemifloxacin is widely distributed throughout the body. Concentrations of gemifloxacin in bronchoalveolar lavage fluid are higher than in plasma. Gemifloxacin penetrates well into lung tissue and pulmonary fluid. Gemifloxacin and its metabolites are excreted via two routes. Following oral administration of gemimifloxacin to healthy subjects, a mean (± standard deviation) 61 ± 9.5% of the dose was excreted unchanged in feces and 36 ± 9.3% in urine. After repeated administration of 320 mg, the mean (± standard deviation) renal clearance was approximately 11.6 ± 3.9 L/hr (range 4.6–17.6 L/hr), indicating that renal excretion of gemimifloxacin involves active secretion. The mean (± standard deviation) plasma elimination half-life at steady state after administration of 320 mg to healthy subjects was approximately 7 ± 2 hours (range 4–12 hours).
Metabolism/Metabolites
Gemifloxacin is primarily metabolized in the liver. All metabolites are produced in low amounts (<10% of the oral dose); major metabolites include N-acetylgemifloxacin, the E-isomer of gemimifloxacin, and carbamoylglucuronide of gemimifloxacin.
The extent of hepatic metabolism of gemimifloxacin is limited. Within 4 hours of administration, the main drug component detected in plasma was the unchanged compound (approximately 65%). All generated metabolites were present in low concentrations (<10% of the orally administered dose); major metabolites included N-acetylgemifloxacin, the E-isomer of gemifloxacin, and carbamoylglucuronide of gemifloxacin. Cytochrome P450 enzymes do not play a significant role in gemifloxacin metabolism, and gemifloxacin does not significantly inhibit the metabolic activity of these enzymes.

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Biological Half-Life
7 (±2) hours
The elimination half-life of gemifloxacin is approximately 7 hours.

Hepatotoxicity
Like other fluoroquinolone drugs, gemifloxacin can cause elevated serum enzymes during treatment, although the incidence may be slightly higher than with placebo or control drugs. These abnormalities are usually mild, asymptomatic, and transient, resolving with continued treatment. Currently reported cases of gemifloxacin-induced hepatotoxicity are too few to reliably describe its clinical characteristics and course. However, liver injury caused by fluoroquinolones appears to be a class effect, and gemifloxacin-induced liver injury also exhibits these characteristics. Cases of liver injury caused by gemifloxacin are much less frequent than those caused by ciprofloxacin, levofloxacin, or moxifloxacin, but they have been reported. Generally, fluoroquinolone-induced hepatotoxicity is characterized by a rapid onset (within days to 3 weeks), often appearing suddenly. Significant nausea, fatigue, abdominal pain, and jaundice are present. The pattern of serum enzyme elevation can be hepatocellular or cholestatic, with shorter-onset cases often being more hepatocellular. ALT levels are significantly elevated, occasionally accompanied by rapid deterioration of prothrombin time and signs of liver failure. Symptoms may appear within days of discontinuation of the drug. Many (but not all) cases experience allergic reactions, manifesting as fever, rash, and eosinophilia. Autoantibodies are usually absent. Probability score: D (Possibly a rare cause of clinically significant liver damage). Pregnancy and Lactation Effects ◉ Overview of Lactation Use Gemifloxacin is not marketed in the United States. There is currently no information on the clinical use of gemifloxacin during lactation; however, the levels in breast milk appear to be very low. Fluoroquinolones are traditionally not used… due to concerns about adverse effects on the developing joints of infants, their use in infants is not recommended. However, recent studies suggest the risk is minimal. Calcium in breast milk may prevent the absorption of small amounts of fluoroquinolones in breast milk, but there is currently insufficient data to confirm or refute this claim. Gemmifloxacin can be used by breastfeeding women. However, it is best to use other medications with known safety information.
◉ Effects on breastfed infants
No relevant published information found as of the revision date.
◉ Effects on lactation and breast milk
No relevant published information found as of the revision date.

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Protein binding rate
60-70%

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Interactions
Drug interactions with warfarin are possible (prothrombin time (PT), international normalized ratio (INR) prolongation and/or bleeding). Infectious diseases and their associated inflammatory processes, age, and general health should be considered. Certain patient factors may also lead to enhanced anticoagulant activity. Closely monitor PT, INR, or other appropriate coagulation tests.
Pharmacokinetic interactions (decreased absorption of gemmifloxacin). Gemmifloxacin should be taken at least 2 hours before taking sucralfate.
Pharmacokinetic interactions with probenecid (decreased clearance of gemmifloxacin).
Pharmacokinetic interactions (decreased absorption of gemmifloxacin). Dietary supplements containing metallic cations such as zinc, magnesium, or iron (e.g., multivitamins, ferrous sulfate) should be taken at least 3 hours before or at least 2 hours after taking gemifloxacin. For more complete data on gemifloxacin interactions (11 items in total), please visit the HSDB records page.

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

Therapeutic Uses

Antimicrobial Drugs
Gemifloxacin is used to treat acute bacterial exacerbations of chronic bronchitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis. /Included on US Product Label/
Gemifloxacin is used to treat mild to moderate community-acquired pneumonia (CAP) caused by susceptible Streptococcus pneumoniae (including multidrug-resistant strains), Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae (formerly known as Chlamydia pneumoniae), or Klebsiella pneumoniae. /Included on US Product Label/

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Drug Warnings
/Black Box Warning/ Warning: Fluoroquinolones (including Factive) are associated with an increased risk of tendinitis and tendon rupture in all age groups. The risk is further increased in older patients (typically over 60 years of age), patients taking corticosteroids, and patients who have received kidney, heart, or lung transplants. /Warning (Black Box)/ Warning: Fluoroquinolones (including Factive) may worsen muscle weakness in patients with myasthenia gravis. Patients with a known history of myasthenia gravis should avoid using Factive. Fluoroquinolones (including gemifloxacin) can cause arthropathy and osteochondropathy in various juvenile animals. The relevance of these adverse reactions observed in juvenile animals to human use is unclear. Fluoroquinolones, including gemifloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups. The risk is higher in older adults (generally those over 60 years of age), patients taking corticosteroids, and kidney, heart, or lung transplant recipients. Other factors that may independently increase the risk of tendon rupture include strenuous exercise, kidney failure, and a history of tendon disease such as rheumatoid arthritis. There have been reports of tendinitis and tendon rupture in patients taking fluoroquinolones even without any of the above risk factors. Fluoroquinolone-related tendinitis and tendon rupture most commonly affect the Achilles tendon and may require surgical repair. In addition, there have been reports of tendinitis and tendon rupture in the rotator cuff (shoulder), hand, biceps, thumb, and other tendon areas. Tendon rupture can occur during or after fluoroquinolone treatment, and has even been reported months after treatment ends. Patients are advised to rest and avoid exercise, and to contact their clinician immediately if they experience the first signs of tendinitis or tendon rupture (e.g., tendon pain, swelling, or inflammation, or joint weakness or inability to move). If tendon pain, swelling, inflammation, or rupture occurs, gemifloxacin should be discontinued.
For more complete data on drug warnings for gemifloxacin (21 in total), please visit the HSDB records page.

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Pharmacodynamics
Gemifloxacin is a quinolone/fluoroquinolone antibiotic. Gemifloxacin has bactericidal activity; its mechanism of action is to bind to an enzyme called DNA gyrase, blocking bacterial DNA replication, thereby unwinding the DNA double helix and preventing it from replicating into two DNA double helices. It is worth noting that this drug has a 100-fold higher affinity for bacterial DNA gyrase than for mammalian DNA gyrase. Gemmifloxacin is a broad-spectrum antibiotic effective 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.)