Inhibiting cell growth and causing cell cycle arrest in the G2/M phase, ciprofloxacin (Bay-09867) monoHClide (5-50 μg/mL; 0-24 hours; tenocytes) is used to treat infections [1]. Yersinia pestis and Bacillus anthracis are effectively inhibited by ciprofloxacin (Bay-09867) monoHClide, demonstrating MIC90 values of 0.03 μg/mL and 0.12 μg/mL, respectively [2].

In a mouse model of pneumonic plague, ciprofloxacin (Bay-09867) monohydrochloride (30 mg/kg; i.p.; 24 hours; BALB/c mice) is protective against Y. pestis [3]. By decreasing LOX levels and raising MMP levels and activity, ciprofloxacin (Bay-09867) monohydrochloride (100 mg/kg; ir; daily for 4 weeks; C57BL/6J mice) accelerates aortic root expansion and raises the risk of aortic dissection and rupture of the aorta wall [4]. Ciprofloxacin (Bay-09867) monoHClide (100 mg/kg; ir; daily for 4 weeks; C57BL/6J mice) causes mitochondrial dysfunction, activation of cytoplasmic DNA sensor signaling, and DNA damage and release into the cytoplasm. Apoptosis and necroptosis in the aorta wall are increased by ciprofloxacin lactate [4].

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

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Cell cycle analysis [1]
Cell Types: Tenocytes
Tested Concentrations: 50 μg/mL
Incubation Duration: 24 hrs (hours)
Experimental Results: The cell cycle was arrested in the G2/M phase and inhibited cell division of tenocytes.

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Western Blot Analysis [1]
Cell Types: tenocytes
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. Upregulates the expression of PLK-1 protein.

Animal/Disease Models: balb/c (Bagg ALBino) mouse [3]
Doses: 30 mg/kg
Route of Administration: intraperitoneal (ip) injection; 24-hour
Experimental Results: diminished the bacterial load in the lungs of the plague mouse model.

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Animal/Disease Models: C57BL/6J mice [4]
Doses: 100 mg/kg
Route of Administration: po (oral gavage); one time/day for 4 weeks
Experimental Results: The aorta was destroyed, accompanied by diminished LOX expression and MMP expression and activity Increase.

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Animal/Disease Models: C57BL/6J mice [4]
Doses: 100 mg/kg
Route of Administration: po (oral gavage); one time/day for 4 weeks
Experimental Results: Causes mitochondrial DNA and nuclear DNA damage, leading to mitochondrial dysfunction and ROS production. Increased aortic wall cell apoptosis and necroptosis.

Absorption, Distribution and Excretion
Following oral administration of 250 mg ciprofloxacin, the mean plasma concentration reached 0.94 mg/L within 0.81 hours, with a mean area under the curve (AUC) of 1.013 L/hkg. The FDA reports oral bioavailability of 70-80%, while other studies report approximately 60%. Early reviews of ciprofloxacin reported oral bioavailability of 64-85%, but recommended 70% bioavailability for all practical applications. 27% of the oral dose is excreted in the urine as unmetabolized form, compared to 46% for intravenously administered doses. Collection results for radiolabeled ciprofloxacin showed a 45% urinary recovery and a 62% fecal recovery. Ciprofloxacin follows a three-compartment distribution model, with a central compartment volume of 0.161 L/kg and a total volume of distribution of 2.00-3.04 L/kg.
After oral administration of 250 mg, the mean renal clearance was 5.08 mL/minkg. After intravenous administration of 100 mg, the mean total clearance was 9.62 mL/minkg, the mean renal clearance was 4.42 mL/minkg, and the mean non-renal clearance was 5.21 mL/minkg.
Based on population pharmacokinetics, the bioavailability of ciprofloxacin oral suspension in children is approximately 60%. In children aged 4 months to 7 years, the mean peak plasma concentration after a single oral dose of 10 mg/kg ciprofloxacin oral suspension was 2.4 μg/mL. No significant age dependence was observed, and peak plasma concentrations did not increase with repeated dosing.
When taken with food, approximately 87% of the drug is slowly released from the tablet over 6 hours. When taken after a meal, peak plasma concentrations are reached approximately 4.5–7 hours after administration. Bioavailability of ProQuin XR tablets is significantly reduced when taken on an empty stomach. In healthy adults, a once-daily dose of 500 mg ProQuin XR extended-release tablets, taken after a meal, resulted in a mean steady-state (day 3) peak plasma concentration of 0.82 μg/mL, reached 6.1 hours after administration. Ciprofloxacin hydrochloride: After oral administration of extended-release tablets containing ciprofloxacin hydrochloride and a base (Cipro XR), peak plasma concentrations of ciprofloxacin are reached within 1–4 hours. Approximately 35% of the dose in Cipro XR tablets is the immediate-release component; the remaining 65% is the extended-release matrix. Steady-state mean peak plasma concentrations of 500 mg ciprofloxacin daily (Cipro XR extended-release tablets) or 250 mg ciprofloxacin twice daily (conventional tablets) were 1.59 μg/mL and 1.14 μg/mL, respectively; however, the area under the concentration-time curve (AUC) was similar for both dosing regimens. Ciprofloxacin Hydrochloride
Peak serum concentrations and AUCs of ciprofloxacin are slightly higher in elderly patients than in younger adults; this may be due to increased bioavailability, reduced volume of distribution, and/or decreased renal clearance in these patients. Single-dose oral studies and single-dose and multiple-dose intravenous studies using standard ciprofloxacin tablets showed that, compared with younger adults, peak plasma concentrations were 16-40% higher, mean AUCs were approximately 30% higher, and elimination half-lifes were approximately 20% longer in individuals aged 65 years and older. These differences are at least partly attributable to decreased renal clearance in this age group and are not clinically significant.
For more complete data on the absorption, distribution, and excretion of ciprofloxacin (18 in total), please visit the HSDB record page.
Metabolism/Metabolites
Ciprofloxacin is primarily metabolized by CYP1A2. The major metabolites, oxociprofloxacin and suciprofloxacin, each account for 3-8% of the total dose. Ciprofloxacin is also converted into minor metabolites, desethyleneciprofloxacin and formylciprofloxacin. These four metabolites account for 15% of the total oral dose. Data on the enzymes and reaction types involved in the formation of these metabolites are currently lacking. The drug is partially metabolized in the liver, where the piperazine group is modified, generating at least four metabolites. These metabolites have been identified as desethyleneciprofloxacin (M1), sulfociprofloxacin (M2), oxociprofloxacin (M3), and N-formylciprofloxacin (M4). Their microbial activity is lower than that of the parent drug, but may be similar to or higher than that of some other quinolones (e.g., M3 and M4 have activity against certain microorganisms comparable to norfloxacin). Hepatic metabolism. Four metabolites have been identified in human urine, accounting for approximately 15% of the total oral dose. The metabolites have antibacterial activity, but lower than that of parent ciprofloxacin. Elimination route: Approximately 40% to 50% of the oral dose is excreted unchanged in the urine.
Half-life: 4 hours

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Biological half-life
The mean half-life after oral administration of 250 mg is 4.71 hours, and the mean half-life after intravenous administration of 100 mg is 3.65 hours. The commonly reported half-life is 4 hours.
The elimination half-life of ciprofloxacin in the serum of adults with normal renal function is 3–7 hours. In healthy adults after intravenous administration, the mean distribution half-life of ciprofloxacin is 0.18–0.37 hours, and the mean elimination half-life is 3–4.8 hours. The elimination half-life of this drug is slightly longer in older adults than in younger adults, with a half-life of 3.3–6.8 hours in adults aged 60–91 years with normal renal function. Based on population pharmacokinetic analysis of pediatric patients with various infections, the predicted mean half-life of ciprofloxacin in children is approximately 4–5 hours. In patients with impaired renal function, serum concentrations of ciprofloxacin are higher, and the half-life is prolonged. In adults with creatinine clearance ≤30 mL/min, the half-life of this drug is 4.4–12.6 hours. Ciprofloxacin half-life: Normal: 4 hours, without renal function: 8.5 hours (Data from table)

Toxicity Summary
Ciprofloxacin's bactericidal effect stems from its inhibition of topoisomerase II (DNA gyrase) and topoisomerase IV, both essential enzymes for bacterial DNA replication, transcription, repair, supercoiling repair, and recombination. Interactions
Serious and even fatal reactions have been reported in patients taking ciprofloxacin and theophylline concurrently. These reactions include cardiac arrest, seizures, status epilepticus, and respiratory failure. While similar serious adverse reactions have been reported in patients taking theophylline alone, the possibility that ciprofloxacin may enhance these reactions cannot be ruled out. If concurrent use cannot be avoided, serum theophylline concentrations should be monitored, and the dose adjusted as needed. The effects of aluminum hydroxide… and calcium carbonate… on the bioavailability of ciprofloxacin were determined in… a three-group randomized crossover study. This study included 12 healthy male volunteers (aged 21-45 years) and included three treatment regimens: 750 mg ciprofloxacin alone, 750 mg ciprofloxacin combined with 3.4 g calcium carbonate or 1.8 g aluminum hydroxide (all taken 5 minutes before ciprofloxacin). When used in combination with calcium carbonate and aluminum hydroxide, the relative bioavailability of ciprofloxacin decreased to 60% and 15% of the control group, respectively. The conclusion is that antacids containing aluminum or calcium should not be taken concurrently with ciprofloxacin.
A patient who had received methadone treatment for more than 6 years with good efficacy experienced deep sedation, confusion, and respiratory depression after taking ciprofloxacin. We believe this is due to ciprofloxacin inhibiting the activity of CYP1A2 and CYP3A4, two cytochrome P450 isoenzymes involved in methadone metabolism. In vitro studies showed no synergistic effect when ciprofloxacin was used in combination with vancomycin against Staphylococcus epidermidis, Staphylococcus aureus (including oxacillin-resistant Staphylococcus aureus), Corynebacterium, or Listeria monocytogenes. For more complete (35) data on drug interactions of ciprofloxacin, please visit the HSDB record page.

[1]. Ciprofloxacin-mediated cell proliferation inhibition and G2/M cell cycle arrest in rat tendon cells. Arthritis Rheum. 2008 Jun;58(6):1657-63.

[2]. 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]. Inhaled Liposomal Ciprofloxacin Protects against a Lethal Infection in a Murine Model of Pneumonic Plague. Front Microbiol. 2017 Feb 6;8:91.

[4]. Effect of Ciprofloxacin on Susceptibility to Aortic Dissection and Rupture in Mice. JAMA Surg. 2018 Sep 1;153(9):e181804.

Therapeutic Uses

Anti-infective drug; Nucleic acid synthesis inhibitor
Ciprofloxacin (intravenous injection, regular tablets, oral suspension) is used to treat bone and joint infections in adults, including osteomyelitis caused by susceptible Enterobacter cloacae, Pseudomonas aeruginosa, or Serratia marcescens. .../US product label includes/
Ciprofloxacin (intravenous injection, regular tablets, oral suspension) is used to treat bone and joint infections in adults, including osteomyelitis caused by susceptible Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, etc. This drug has also been used to treat bone and joint infections in adults caused by susceptible Staphylococcus aureus, Staphylococcus epidermidis, other coagulase-negative staphylococci, or Enterococcus faecalis (formerly known as Enterococcus faecalis), but other anti-infective drugs are usually the first choice. Although some oxacillin-resistant Staphylococcus aureus strains have been reported to be resistant to ciprofloxacin, oral ciprofloxacin may be an effective alternative therapy for infections caused by susceptible oxacillin-resistant Staphylococcus aureus without the need for parenteral antibiotics. /Not included in US product label/
Despite limited experience to date, the American Heart Association (AHA) and the Infectious Diseases Society of America (IDSA) recommend ciprofloxacin as an alternative treatment for natural or artificial valvular endocarditis caused by HACEK group (Actinomyces actinomycetii, Cardiobacterium hominis, Ekenella corrosiformis, Haemophilus influenzae, Haemophilus parainfluenzae, Haemophilus parasuis, Denitrifying Kydonia, and Kydonia kiuridis). /Not included in US product label/
For more complete data on the therapeutic uses of ciprofloxacin (out of 53), please visit the HSDB record page.

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Drug Warning
/Black Box Warning/ Warning: Fluoroquinolones, including ciprofloxacin, increase the 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.
/Black Box Warning/ Warning: Fluoroquinolones, including ciprofloxacin, may worsen muscle weakness symptoms in patients with myasthenia gravis. Ciprofloxacin should be avoided in patients with a known history of myasthenia gravis.
In four corneal transplant patients treated preoperatively with ciprofloxacin eye drops, two developed microprecipitates associated with damaged corneal epithelium. Another patient developed a large amount of precipitation at the site of a corneal ulcer. All specimens were examined using electron microscopy and high-performance liquid chromatography. The crystalline precipitate was pure ciprofloxacin. On agar plates inoculated with susceptible bacteria, the large amount of precipitate showed large zones of inhibition at both 24 and 48 hours. In vitro studies have demonstrated its biological activity and bioavailability. Severe and even fatal hypersensitivity reactions (anaphylactic shock) have been reported in patients treated with quinolone drugs, some occurring after the first dose. Some reactions are accompanied by cardiovascular failure, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and pruritus. Only a small number of patients have a history of hypersensitivity reactions. Severe anaphylactic shock requires immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including endotracheal intubation, should be administered as needed. For more complete data on drug warnings for ciprofloxacin (41 in total), please visit the HSDB records page. Pharmacodynamics: Ciprofloxacin is a second-generation fluoroquinolone drug effective against a wide range of Gram-negative and Gram-positive bacteria. Its mechanism of action is through inhibition of bacterial DNA gyrase and topoisomerase IV. Ciprofloxacin has an affinity for bacterial DNA gyrase that is 100 times greater than that for mammalian DNA gyrase. Fluoroquinolones do not exhibit cross-resistance with other classes of antibiotics, therefore ciprofloxacin may have clinical value when other antibiotics become ineffective. Ciprofloxacin and its derivatives are also being investigated for the treatment of malaria, cancer, and HIV/AIDS.

C17H19CLFN3O3

367.8025

367.109

93107-08-5

Ciprofloxacin;85721-33-1;Ciprofloxacin hydrochloride monohydrate;86393-32-0;Ciprofloxacin-d8 hydrochloride hydrate

2764

White to off-white solid powder

581.8ºC at 760 mmHg

>300ºC

305.6ºC

2.779

2

7

3

24

571

0

MYSWGUAQZAJSOK-UHFFFAOYSA-N

InChI=1S/C17H18FN3O3/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)

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

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.  (2). This product is not stable in solution, please use freshly prepared working solution for optimal results.

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

H2O : ~12.5 mg/mL (~33.99 mM)
DMSO : ~5 mg/mL (~13.59 mM)

Solubility in Formulation 1: ≥ 0.5 mg/mL (1.36 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 2: ≥ 0.5 mg/mL (1.36 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.)