The primary targets of ciprofloxacin are bacterial DNA gyrase (encoded by gyrA and gyrB) and topoisomerase IV (parC and parE). These enzymes are responsible for maintaining DNA supercoiling and decatenation during replication. Ciprofloxacin binds to the enzyme-DNA complex, stabilizing the cleaved DNA complex and preventing relegation, which leads to double-strand breaks and ultimately bacterial cell death. It has high affinity for DNA gyrase in Gram-negative bacteria and topoisomerase IV in Gram-positive bacteria. The drug's selectivity for bacterial enzymes over mammalian topoisomerases is due to structural differences, which accounts for its low toxicity to host cells.

In tendon cells, ciprofloxacin (Bay-09867) hydrochloride monohydrate (5–50 μg/mL; 0–24 h) suppresses cell growth and induces cell cycle arrest at the G2/M phase[1]. With MIC90s of 0.03 μg/mL and 0.12 μg/mL, respectively, ciprofloxacin (Bay-09867) hydrochloride monohydrate exhibits strong action against Y. pestis and B. anthracis[2].
In vitro, ciprofloxacin demonstrates potent antibacterial activity with minimum inhibitory concentrations (MIC90) of ≤0.25 µg/mL for most Enterobacteriaceae, ≤1 µg/mL for Pseudomonas aeruginosa, and ≤2 µg/mL for Staphylococcus aureus. It is bactericidal and shows concentration-dependent killing. It also exhibits activity against atypical pathogens like Chlamydia, Mycoplasma, and Legionella. It is often used in combination with other antibiotics for synergy. The emergence of resistance is primarily due to mutations in the target enzymes or efflux pumps. Its activity is assessed by broth microdilution or agar dilution methods following CLSI guidelines.

Y is protected from by ciprofloxacin (Bay-09867) hydrochloride monohydrate (30 mg/kg; ip; for 24 hours; BALB/c mice). pestis in the pneumonic plague model in mice[3]. By lowering LOX levels and raising MMP levels and activity in the aorta wall, ciprofloxacin (Bay-09867) hydrochloride monohydrate (100 mg/kg; ig; daily, for 4 weeks; C57BL/6J mice) accelerates aortic root expansion and raises the incidence of aortic dissection and rupture[4]. Ciprofloxacin (Bay-09867) hydrochloride monohydrate (100 mg/kg; ig; daily, for 4 weeks; C57BL/6J mice) causes mitochondrial dysfunction, cytosolic DNA sensor signaling activation, and DNA damage and release into the cytosol. Apoptosis and necroptosis in the aortic wall are increased by ciprofloxacin lactate[4].
In vivo, ciprofloxacin is highly effective against systemic infections in animal models, such as murine sepsis caused by E. coli or Pseudomonas. It achieves good tissue penetration, including into the lung, kidney, prostate, and bone. In clinical settings, it is used for urinary tract infections, respiratory infections, gastrointestinal infections, and bone and joint infections. Its oral bioavailability (70-80%) allows for intravenous-to-oral switch therapy. It is also used as prophylaxis for anthrax and as a treatment for plague. Its clinical efficacy has been established in numerous randomized controlled trials.

The antibacterial activity of ciprofloxacin is assessed using standard susceptibility testing methods. For cell-free enzyme assays, DNA gyrase supercoiling activity is measured using a plasmid DNA substrate and ATP; inhibition by ciprofloxacin is quantified by agarose gel electrophoresis. Alternatively, DNA cleavage complex formation can be monitored using radiolabeled DNA. These cell-free assays allow precise determination of IC50 values and elucidation of the mechanism of action. For routine testing, the broth microdilution method in cation-adjusted Mueller-Hinton broth is used to determine MICs.

Cell Viability Assay[1]
Cell Types: Tendon cells
Tested Concentrations: 5, 10, 20 and 50 μg /mL
Incubation Duration: 24 hrs (hours)
Experimental Results: diminished the cellularity of tendon cells.

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Cell Cycle Analysis[1]
Cell Types: Tendon cells
Tested Concentrations: 50 μg/mL
Incubation Duration: 24 hrs (hours)
Experimental Results: Arrested cell cycle at the G2/M phase and inhibited cell division in tendon cells.

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Western Blot Analysis[1]
Cell Types: Tendon cells
Tested Concentrations: 50 μg/mL
Incubation Duration: 0, 6, 12, 17 and 24 hrs (hours)
Experimental Results: Down-regulated the expression of CDK-1 and cyclin B protein and mRNA. Up-regulated the expression of PLK-1 protein.
In cellular assays, ciprofloxacin's activity is evaluated in infected cell lines, such as macrophages infected with intracellular Salmonella or Chlamydia. The drug's ability to reduce intracellular bacterial counts is measured by colony counting after cell lysis. Additionally, its effect on eukaryotic cell lines (e.g., HepG2, Vero) is assessed for cytotoxicity, which is minimal at therapeutic concentrations. In cancer research, ciprofloxacin has been shown to induce apoptosis in some cancer cell lines, but this is not a primary clinical use. The compound's uptake and efflux in mammalian cells can be studied using radiolabeled drug.

Animal/Disease Models: balb/c (Bagg ALBino) mouse[3]
Doses: 30 mg/kg
Route of Administration: intraperitoneal (ip)injection; for 24 hrs (hours)
Experimental Results: decreased the lung bacterial load in murine model of pneumonic plague.

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Animal/Disease Models: C57BL/6J mice[4]
Doses: 100 mg/kg
Route of Administration: po (oral gavage); daily, for 4 weeks
Experimental Results: Had aortic destruction that was accompanied by diminished LOX expression and increased MMP expression and activity.

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Animal/Disease Models: C57BL/ 6J mice[4]
Doses: 100 mg/kg
Route of Administration: po (oral gavage); daily, for 4 weeks
Experimental Results: Caused mitochondrial DNA and nuclear DNA damage, leading to mitochondrial dysfunction and ROS production. Increased apoptosis and necroptosis in the aortic wall.
Animal models for efficacy include the neutropenic mouse thigh infection model, which is used to correlate pharmacokinetic/pharmacodynamic (PK/PD) parameters with efficacy. Mice are infected intramuscularly with a bacterial strain, and ciprofloxacin is administered subcutaneously or orally at various doses. The reduction in colony-forming units (CFU) per thigh is measured after 24 hours. Other models include pneumonia, pyelonephritis, and sepsis. These studies help determine the dose needed to achieve target exposures (AUC/MIC ratio > 125 for Gram-negative bacteria). Pharmacodynamic studies also assess the post-antibiotic effect.

Ciprofloxacin is well absorbed orally (70-80% bioavailability) with a half-life of about 4 hours in humans. It is extensively distributed into tissues, with high concentrations in urine, bile, prostate, and lung. It is metabolized partially to four metabolites, with 40-50% excreted unchanged in urine. In animals, similar PK profiles are observed, but clearance may be faster in rodents. Its protein binding is low (20-40%). For in vivo research, ciprofloxacin is often given in drinking water or by gavage. The presence of divalent cations (e.g., in milk) reduces absorption, so dosing should be separated from feed.

Effects During Pregnancy and Lactation
◉ Overview of Medication Use During Lactation
The concentration of ciprofloxacin in breast milk is very low. Traditionally, fluoroquinolones (such as ciprofloxacin) are not recommended for use in infants due to concerns about adverse effects on the developing joints of infants. However, studies have shown that the risk is minimal. Calcium in breast milk may reduce the absorption of small amounts of fluoroquinolones in breast milk, but there is currently insufficient data to confirm or refute this claim. Breastfeeding women can use ciprofloxacin, but close monitoring of the infant's gut microbiota is necessary, for example, for changes in diarrhea or candidiasis (thrush, diaper rash). Avoiding breastfeeding for 3 to 4 hours after taking ciprofloxacin can reduce the amount of ciprofloxacin the infant is exposed to through breast milk.
The risk to a breastfeeding infant from the mother's use of ear drops or eye drops containing ciprofloxacin is negligible. After using eye drops, to significantly reduce the amount of medication entering breast milk, press the tear duct near the corner of the eye for 1 minute or longer, then wipe away excess medication with absorbent tissue.
◉ Effects on breastfed infants
A 2-month-old breastfed infant with a history of necrotizing enterocolitis developed pseudomembranous colitis, most likely due to the mother's self-treatment with ciprofloxacin.
Ciprofloxacin was used as part of a multidrug regimen to treat three pregnant women with multidrug-resistant tuberculosis throughout pregnancy and postpartum. All three infants were breastfed (the extent and duration of breastfeeding were not specified). At 1.25, 1.8, and 3.9 years of age, all but one child showed normal development; the growth retardation was likely due to postnatal tuberculosis infection.
◉ Effects on breastfeeding and breast milk
No relevant published information was found as of the revision date.
Ciprofloxacin is generally well tolerated, but adverse effects include gastrointestinal upset, CNS effects (dizziness, headache), and arthropathy in juvenile animals. It is not recommended in children or pregnant women due to cartilage damage. Hypersensitivity reactions and phototoxicity are also reported. In animal studies, high doses cause crystalluria and nephrotoxicity. The safety margin is moderate; the therapeutic index is approximately 10-20 in humans. It is a substrate for CYP450, but minimal interactions occur. Toxicity is often evaluated in repeat-dose studies in rats and dogs, where the no-observed-adverse-effect level (NOAEL) is determined.

[1]. Tsai WC, et, al. Ciprofloxacin-mediated cell proliferation inhibition and G2/M cell cycle arrest in rat tendon cells. Arthritis Rheum. 2008 Jun;58(6):1657-63.
[2]. Steenbergen J, et, al. In Vitro and In Vivo Activity of Omadacycline against Two Biothreat Pathogens, Bacillus anthracis and Yersinia pestis. Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02434-16.
[3]. Hamblin KA, et, al. Inhaled Liposomal Ciprofloxacin Protects against a Lethal Infection in a Murine Model of Pneumonic Plague. Front Microbiol. 2017 Feb 6;8:91.
[4]. LeMaire SA, et, al. Effect of Ciprofloxacin on Susceptibility to Aortic Dissection and Rupture in Mice. JAMA Surg. 2018 Sep 1;153(9):e181804.

Ciprofloxacin hydrochloride hydrate is the monohydrate form of ciprofloxacin hydrochloride. It is an EC 5.99.1.3 [DNA topoisomerase (ATP hydrolysis)] inhibitor with antibacterial, topoisomerase IV inhibitor, and anti-infective effects. It contains anhydrous ciprofloxacin hydrochloride. Ciprofloxacin is a prescription antimicrobial drug approved by the U.S. Food and Drug Administration (FDA) for the treatment and prevention of various infections caused by certain bacteria, such as certain urinary tract infections, lower respiratory tract infections, and skin infections. Some bacterial infections may be opportunistic infections (OIs) associated with HIV. Opportunistic infections (OIs) are infections that are more common or more severe in people with weakened immune systems (such as HIV-infected individuals) than in people with healthy immune systems. Ciprofloxacin hydrochloride is the hydrochloride form of ciprofloxacin, a fluoroquinolone antimicrobial drug associated with nalidixic acid. Ciprofloxacin hydrochloride exerts its bactericidal effect by interfering with bacterial DNA gyrase, thereby inhibiting DNA synthesis and preventing bacterial cell growth.
A broad-spectrum antibacterial carboxyfluoroquinolone drug.
See also: Ciprofloxacin (containing the active ingredient); Ciprofloxacin; Ciprofloxacin hydrochloride (ingredient); Ciprofloxacin hydrochloride; Hydrocortisone (ingredient)...See more...

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Drug Indications
Treatment of chronic lung infections caused by Pseudomonas aeruginosa.
Ciprofloxacin is a World Health Organization Essential Medicine, widely prescribed for many bacterial infections. It is available in multiple formulations (tablets, IV, eye drops, ear drops). Its development in the 1980s marked a major advance in antibiotic therapy. Resistance has emerged, but it remains a key drug for complicated UTIs and anthrax. It is also used in veterinary medicine. Research continues on its potential immunomodulatory and anticancer properties, though these are not clinically exploited. It is off-patent and generically available.

C17H21CLFN3O4MOLECULARWEIGHT

385.8177

385.12

86393-32-0

Ciprofloxacin;85721-33-1;Ciprofloxacin monohydrochloride;93107-08-5;Ciprofloxacin-d8 hydrochloride monohydrate

62998

White to off-white solid powder

581.8ºC at 760 mmHg

318-320 °C

305.6ºC

2.714

4

8

3

26

571

0

Cl.O=C(C1C(=O)C2C(=CC(N3CCNCC3)=C(C=2)F)N(C2CC2)C=1)O.O

ARPUHYJMCVWYCZ-UHFFFAOYSA-N

InChI=1S/C17H18FN3O3.ClH.H2O/c18-13-7-11-14(8-15(13)20-5-3-19-4-6-20)21(10-1-2-10)9-12(16(11)22)17(23)24;;/h7-10,19H,1-6H2,(H,23,24);1H;1H2

1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid;hydrate;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

DMSO : ~5 mg/mL (~12.96 mM)

Solubility in Formulation 1: ≥ 0.5 mg/mL (1.30 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 5.0 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.

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Solubility in Formulation 2: ≥ 0.5 mg/mL (1.30 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 5.0 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.

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Solubility in Formulation 3: ≥ 0.5 mg/mL (1.30 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 5.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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