CIPROFLOXACIN

EC / List no.: 617-751-0
CAS no.: 85721-33-1
Mol. formula: C17H18FN3O3

Ciprofloxacin is a fluoroquinolone (flor-o-KWIN-o-lone) antibiotic used to treat a number of bacterial infections.
This includes bone and joint infections, intra abdominal infections, certain type of infectious diarrhea, respiratory tract infections, skin infections, typhoid fever, and urinary tract infections, among others.
For some infections Ciprofloxacin is used in addition to other antibiotics.
Ciprofloxacin can be taken by mouth, as eye drops, as ear drops, or intravenously.

Common side effects include nausea, vomiting, and diarrhea.
Severe side effects include an increased risk of tendon rupture, hallucinations, and nerve damage.
In people with myasthenia gravis, there is worsening muscle weakness.
Rates of side effects appear to be higher than some groups of antibiotics such as cephalosporins but lower than others such as clindamycin.
Studies in other animals raise concerns regarding use in pregnancy.
No problems were identified, however, in the children of a small number of women who took the medication.
Ciprofloxacin appears to be safe during breastfeeding.
Ciprofloxacin is a second-generation fluoroquinolone with a broad spectrum of activity that usually results in the death of the bacteria.

Ciprofloxacin was patented in 1980 and introduced in 1987.
Ciprofloxacin is on the World Health Organization's List of Essential Medicines.
The World Health Organization classifies ciprofloxacin as critically important for human medicine.
Ciprofloxacin is available as a generic medication.
In 2019, it was the 113th most commonly prescribed medication in the United States, with more than 5 million prescriptions.

Medical uses
Ciprofloxacin is used to treat a wide variety of infections, including infections of bones and joints, endocarditis, gastroenteritis, malignant otitis externa, respiratory tract infections, cellulitis, urinary tract infections, prostatitis, anthrax, and chancroid.

Ciprofloxacin only treats bacterial infections; it does not treat viral infections such as the common cold. 
For certain uses including acute sinusitis, lower respiratory tract infections and uncomplicated gonorrhea, ciprofloxacin is not considered a first-line agent.

Ciprofloxacin occupies an important role in treatment guidelines issued by major medical societies for the treatment of serious infections, especially those likely to be caused by Gram-negative bacteria, including Pseudomonas aeruginosa. 
For example, ciprofloxacin in combination with metronidazole is one of several first-line antibiotic regimens recommended by the Infectious Diseases Society of America for the treatment of community-acquired abdominal infections in adults.
Ciprofloxacin also features prominently in treatment guidelines for acute pyelonephritis, complicated or hospital-acquired urinary tract infection, acute or chronic prostatitis, certain types of endocarditis, certain skin infections, and prosthetic joint infections.

In other cases, treatment guidelines are more restrictive, recommending in most cases that older, narrower-spectrum drugs be used as first-line therapy for less severe infections to minimize fluoroquinolone-resistance development. 
For example, the Infectious Diseases Society of America recommends the use of ciprofloxacin and other fluoroquinolones in urinary tract infections be reserved to cases of proven or expected resistance to narrower-spectrum drugs such as nitrofurantoin or trimethoprim/sulfamethoxazole.
The European Association of Urology recommends ciprofloxacin as an alternative regimen for the treatment of uncomplicated urinary tract infections, but cautions that the potential for "adverse events have to be considered".

Although approved by regulatory authorities for the treatment of respiratory infections, ciprofloxacin is not recommended for respiratory infections by most treatment guidelines due in part to its modest activity against the common respiratory pathogen Streptococcus pneumoniae.
"Respiratory quinolones" such as levofloxacin, having greater activity against this pathogen, are recommended as first line agents for the treatment of community-acquired pneumonia in patients with important co-morbidities and in patients requiring hospitalization (Infectious Diseases Society of America 2007). 
Similarly, ciprofloxacin is not recommended as a first-line treatment for acute sinusitis.

Ciprofloxacin is approved for the treatment of gonorrhea in many countries, but this recommendation is widely regarded as obsolete due to resistance development.

Pregnancy
In the United States ciprofloxacin is pregnancy category C.
This category includes drugs for which no adequate and well-controlled studies in human pregnancy exist, and for which animal studies have suggested the potential for harm to the fetus, but potential benefits may warrant use of the drug in pregnant women despite potential risks. 
An expert review of published data on experiences with ciprofloxacin use during pregnancy by the Teratogen Information System concluded therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (quantity and quality of data=fair), but the data are insufficient to state no risk exists.
Exposure to quinolones, including levofloxacin, during the first-trimester is not associated with an increased risk of stillbirths, premature births, birth defects, or low birth weight.

Two small post-marketing epidemiology studies of mostly short-term, first-trimester exposure found that fluoroquinolones did not increase risk of major malformations, spontaneous abortions, premature birth, or low birth weight.
The label notes, however, that these studies are insufficient to reliably evaluate the definitive safety or risk of less common defects by ciprofloxacin in pregnant women and their developing fetuses.

Breastfeeding
Fluoroquinolones have been reported as present in a mother's milk and thus passed on to the nursing child.
The U.S. Food and Drug Administration (FDA) recommends that because of the risk of serious adverse reactions (including articular damage) in infants nursing from mothers taking ciprofloxacin, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Children
Oral and intravenous ciprofloxacin are approved by the FDA for use in children for only two indications due to the risk of permanent injury to the musculoskeletal system:

Inhalational anthrax (postexposure)
Complicated urinary tract infections and pyelonephritis due to Escherichia coli, but never as first-line agents.
Current recommendations by the American Academy of Pediatrics note the systemic use of ciprofloxacin in children should be restricted to infections caused by multidrug-resistant pathogens or when no safe or effective alternatives are available.

Spectrum of activity
Its spectrum of activity includes most strains of bacterial pathogens responsible for community-acquired pneumonias, bronchitis, urinary tract infections, and gastroenteritis.
Ciprofloxacin is particularly effective against Gram-negative bacteria (such as Escherichia coli, Haemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Moraxella catarrhalis, Proteus mirabilis, and Pseudomonas aeruginosa), but is less effective against Gram-positive bacteria (such as methicillin-sensitive Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis) than newer fluoroquinolones.

Bacterial resistance
See also: Antibiotic abuse and Antibiotic resistance
As a result of its widespread use to treat minor infections readily treatable with older, narrower spectrum antibiotics, many bacteria have developed resistance to this drug in recent years, leaving it significantly less effective than it would have been otherwise.

Resistance to ciprofloxacin and other fluoroquinolones may evolve rapidly, even during a course of treatment. 
Numerous pathogens, including enterococci, Streptococcus pyogenes and Klebsiella pneumoniae (quinolone-resistant) now exhibit resistance.
Widespread veterinary usage of the fluoroquinolones, particularly in Europe, has been implicated.
Meanwhile, some Burkholderia cepacia, Clostridium innocuum and Enterococcus faecium strains have developed resistance to ciprofloxacin to varying degrees.

Fluoroquinolones had become the class of antibiotics most commonly prescribed to adults in 2002.
Nearly half (42%) of those prescriptions in the U.S. were for conditions not approved by the FDA, such as acute bronchitis, otitis media, and acute upper respiratory tract infection, according to a study supported in part by the Agency for Healthcare Research and Quality.
Additionally, they were commonly prescribed for medical conditions that were not even bacterial to begin with, such as viral infections, or those to which no proven benefit existed.

Adverse effects
Adverse effects can involve the tendons, muscles, joints, nerves, and the central nervous system.

Rates of adverse effects appear to be higher than with some groups of antibiotics such as cephalosporins but lower than with others such as clindamycin.
Compared to other antibiotics some studies find a higher rate of adverse effects while others find no difference.
In clinical trials most of the adverse events were described as mild or moderate in severity, abated soon after the drug was discontinued, and required no treatment.
Some adverse effects may be permanent.
Ciprofloxacin was stopped because of an adverse event in 1% of people treated with the medication by mouth. 
The most frequently reported drug-related events, from trials of all formulations, all dosages, all drug-therapy durations, and for all indications, were nausea (2.5%), diarrhea (1.6%), abnormal liver function tests (1.3%), vomiting (1%), and rash (1%). Other adverse events occurred at rates of <1%.

Tendon problems
Ciprofloxacin includes a boxed warning in the United States due to an increased risk of tendinitis and tendon rupture, especially in people who are older than 60 years, people who also use corticosteroids, and people with kidney, lung, or heart transplants.
Tendon rupture can occur during therapy or even months after discontinuation of the medication.
One study found that fluoroquinolone use was associated with a 1.9-fold increase in tendon problems. 
The risk increased to 3.2 in those over 60 years of age and to 6.2 in those over the age of 60 who were also taking corticosteroids. 
Among the 46,766 quinolone users in the study, 38 (0.08%) cases of Achilles tendon rupture were identified.

Cardiac arrhythmia
The fluoroquinolones, including ciprofloxacin, are associated with an increased risk of cardiac toxicity, including QT interval prolongation, torsades de pointes, ventricular arrhythmia, and sudden death.

Nervous system
Because Ciprofloxacin is lipophilic, it has the ability to cross the blood-brain barrier.
The 2013 FDA label warns of nervous system effects. 
Ciprofloxacin, like other fluoroquinolones, is known to trigger seizures or lower the seizure threshold, and may cause other central nervous system adverse effects. 
Headache, dizziness, and insomnia have been reported as occurring fairly commonly in postapproval review articles, along with a much lower incidence of serious CNS adverse effects such as tremors, psychosis, anxiety, hallucinations, paranoia, and suicide attempts, especially at higher doses.
Like other fluoroquinolones, it is also known to cause peripheral neuropathy that may be irreversible, such as weakness, burning pain, tingling or numbness.

Cancer
Ciprofloxacin is active in six of eight in vitro assays used as rapid screens for the detection of genotoxic effects, but is not active in in vivo assays of genotoxicity.
Long-term carcinogenicity studies in rats and mice resulted in no carcinogenic or tumorigenic effects due to ciprofloxacin at daily oral dose levels up to 250 and 750 mg/kg to rats and mice, respectively (about 1.7 and 2.5 times the highest recommended therapeutic dose based upon mg/m2). 
Results from photo co-carcinogenicity testing indicate ciprofloxacin does not reduce the time to appearance of UV-induced skin tumors as compared to vehicle control.

Other
The other black box warning is that ciprofloxacin should not be used in people with myasthenia gravis due to possible exacerbation of muscle weakness which may lead to breathing problems resulting in death or ventilator support. 
Fluoroquinolones are known to block neuromuscular transmission.
There are concerns that fluoroquinolones including ciprofloxacin can affect cartilage in young children.

Clostridium difficile-associated diarrhea is a serious adverse effect of ciprofloxacin and other fluoroquinolones; it is unclear whether the risk is higher than with other broad-spectrum antibiotics.

A wide range of rare but potentially fatal adverse effects reported to the U.S. FDA or the subject of case reports includes aortic dissection, toxic epidermal necrolysis, Stevens–Johnson syndrome, low blood pressure, allergic pneumonitis, bone marrow suppression, hepatitis or liver failure, and sensitivity to light.
The medication should be discontinued if a rash, jaundice, or other sign of hypersensitivity occurs.

Children and the elderly are at a much greater risk of experiencing adverse reactions.

Overdose
Overdose of ciprofloxacin may result in reversible renal toxicity. 
Treatment of overdose includes emptying of the stomach by induced vomiting or gastric lavage, as well as administration of antacids containing magnesium, aluminium, or calcium to reduce drug absorption. 
Renal function and urinary pH should be monitored. 
Important support includes adequate hydration and urine acidification if necessary to prevent crystalluria. 
Hemodialysis or peritoneal dialysis can only remove less than 10% of ciprofloxacin.
Ciprofloxacin may be quantified in plasma or serum to monitor for drug accumulation in patients with hepatic dysfunction or to confirm a diagnosis of poisoning in acute overdose victims.

Interactions
Ciprofloxacin interacts with certain foods and several other drugs leading to undesirable increases or decreases in the serum levels or distribution of one or both drugs.

Ciprofloxacin should not be taken with antacids containing magnesium or aluminum, highly buffered drugs (sevelamer, lanthanum carbonate, sucralfate, didanosine), or with supplements containing calcium, iron, or zinc. 
Ciprofloxacin should be taken two hours before or six hours after these products. 
Magnesium or aluminum antacids turn ciprofloxacin into insoluble salts that are not readily absorbed by the intestinal tract, reducing peak serum concentrations by 90% or more, leading to therapeutic failure.
Additionally, it should not be taken with dairy products or calcium-fortified juices alone, as peak serum concentration and the area under the serum concentration-time curve can be reduced up to 40%. However, ciprofloxacin may be taken with dairy products or calcium-fortified juices as part of a meal.

Ciprofloxacin inhibits the drug-metabolizing enzyme CYP1A2 and thereby can reduce the clearance of drugs metabolized by that enzyme. 
CYP1A2 substrates that exhibit increased serum levels in ciprofloxacin-treated patients include tizanidine, theophylline, caffeine, methylxanthines, clozapine, olanzapine, and ropinirole. 
Co-administration of ciprofloxacin with the CYP1A2 substrate tizanidine (Zanaflex) is contraindicated due to a 583% increase in the peak serum concentrations of tizanidine when administered with ciprofloxacin as compared to administration of tizanidine alone. 
Use of ciprofloxacin is cautioned in patients on theophylline due to its narrow therapeutic index. 
The authors of one review recommended that patients being treated with ciprofloxacin reduce their caffeine intake. 
Evidence for significant interactions with several other CYP1A2 substrates such as cyclosporine is equivocal or conflicting.

The Committee on Safety of Medicines and the FDA warn that central nervous system adverse effects, including seizure risk, may be increased when NSAIDs are combined with quinolones.
The mechanism for this interaction may involve a synergistic increased antagonism of GABA neurotransmission.

Altered serum levels of the antiepileptic drugs phenytoin and carbamazepine (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin.
Ciprofloxacin is a potent inhibitor of CYP1A2, CYP2D6, and CYP3A4.

Mechanism of action
Ciprofloxacin is a broad-spectrum antibiotic of the fluoroquinolone class. 
Ciprofloxacin is active against some Gram-positive and many Gram-negative bacteria.
Ciprofloxacin functions by inhibiting a type II topoisomerase (DNA gyrase) and topoisomerase IV, necessary to separate bacterial DNA, thereby inhibiting cell division.

Pharmacokinetics
Ciprofloxacin for systemic administration is available as immediate-release tablets, extended-release tablets, an oral suspension, and as a solution for intravenous administration. 
When administered over one hour as an intravenous infusion, ciprofloxacin rapidly distributes into the tissues, with levels in some tissues exceeding those in the serum. 
Penetration into the central nervous system is relatively modest, with cerebrospinal fluid levels normally less than 10% of peak serum concentrations. 
The serum half-life of ciprofloxacin is about 4–6 hours, with 50–70% of an administered dose being excreted in the urine as unmetabolized drug. 
An additional 10% is excreted in urine as metabolites. 
Urinary excretion is virtually complete 24 hours after administration. 
Dose adjustment is required in the elderly and in those with renal impairment.

Ciprofloxacin is weakly bound to serum proteins (20–40%), but is an inhibitor of the drug-metabolizing enzyme cytochrome P450 1A2, which leads to the potential for clinically important drug interactions with drugs metabolized by that enzyme.

Ciprofloxacin is about 70% orally available when administered orally, so a slightly higher dose is needed to achieve the same exposure when switching from IV to oral administration

The extended release oral tablets allow once-daily administration by releasing the drug more slowly in the gastrointestinal tract. 
These tablets contain 35% of the administered dose in an immediate-release form and 65% in a slow-release matrix. 
Maximum serum concentrations are achieved between 1 and 4 hours after administration. 
Compared to the 250- and 500-mg immediate-release tablets, the 500-mg and 1000-mg XR tablets provide higher Cmax, but the 24‑hour AUCs are equivalent.

Ciprofloxacin immediate-release tablets contain ciprofloxacin as the hydrochloride salt, and the XR tablets contain a mixture of the hydrochloride salt as the free base.

Chemical properties
Ciprofloxacin is 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid.
Its empirical formula is C17H18FN3O3 and its molecular weight is 331.4 g/mol.
Ciprofloxacin is a faintly yellowish to light yellow crystalline substance.

Ciprofloxacin hydrochloride (USP) is the monohydrochloride monohydrate salt of ciprofloxacin. 
Ciprofloxacin is a faintly yellowish to light yellow crystalline substance with a molecular weight of 385.8 g/mol. 
Its empirical formula is C17H18FN3O3HCl•H2O.

Usage
Ciprofloxacin is the most widely used of the second-generation quinolones.
In 2010, over 20 million prescriptions were written, making it the 35th-most commonly prescribed generic drug and the 5th-most commonly prescribed antibacterial in the U.S.

History
The first members of the quinolone antibacterial class were relatively low-potency drugs such as nalidixic acid, used mainly in the treatment of urinary tract infections owing to their renal excretion and propensity to be concentrated in urine.
In 1979, the publication of a patent filed by the pharmaceutical arm of Kyorin Seiyaku Kabushiki Kaisha disclosed the discovery of norfloxacin, and the demonstration that certain structural modifications including the attachment of a fluorine atom to the quinolone ring leads to dramatically enhanced antibacterial potency.
In the aftermath of this disclosure, several other pharmaceutical companies initiated research and development programs with the goal of discovering additional antibacterial agents of the fluoroquinolone class.

The fluoroquinolone program at Bayer focused on examining the effects of very minor changes to the norfloxacin structure.
In 1983, the company published in vitro potency data for ciprofloxacin, a fluoroquinolone antibacterial having a chemical structure differing from that of norfloxacin by the presence of a single carbon atom.
This small change led to a two- to 10-fold increase in potency against most strains of Gram-negative bacteria. 
Importantly, this structural change led to a four-fold improvement in activity against the important Gram-negative pathogen Pseudomonas aeruginosa, making ciprofloxacin one of the most potent known drugs for the treatment of this intrinsically antibiotic-resistant pathogen.

The oral tablet form of ciprofloxacin was approved in October 1987, just one year after the approval of norfloxacin.
In 1991, the intravenous formulation was introduced. 
Ciprofloxacin sales reached a peak of about 2 billion euros in 2001, before Bayer's patent expired in 2004, after which annual sales have averaged around €200 million.

The name probably originates from the International Scientific Nomenclature: ci- (alteration of cycl-) + propyl + fluor- + ox- + az- + -mycin.

Society and culture
Cost
Ciprofloxacin is available as a generic medication and not very expensive.
At least One company, Turtle Pharma Private Limited provides industrial-size amounts

Generic equivalents
On 24 October 2001, the Prescription Access Litigation (PAL) project filed suit to dissolve an agreement between Bayer and three of its competitors which produced generic versions of drugs (Barr Laboratories, Rugby Laboratories, and Hoechst-Marion-Roussel) that PAL claimed was blocking access to adequate supplies and cheaper, generic versions of ciprofloxacin. 
The plaintiffs charged that Bayer Corporation, a unit of Bayer AG, had unlawfully paid the three competing companies a total of $200 million to prevent cheaper, generic versions of ciprofloxacin from being brought to the market, as well as manipulating its price and supply. 
Numerous other consumer advocacy groups joined the lawsuit. 
On 15 October 2008, five years after Bayer's patent had expired, the United States District Court for the Eastern District of New York granted Bayer's and the other defendants' motion for summary judgment, holding that any anticompetitive effects caused by the settlement agreements between Bayer and its codefendants were within the exclusionary zone of the patent and thus could not be redressed by federal antitrust law, in effect upholding Bayer's agreement with its competitors.

Available forms
Ciprofloxacin for systemic administration is available as immediate-release tablets, as extended-release tablets, as an oral suspension, and as a solution for intravenous infusion. 
Ciprofloxacin is also available for local administration as eye drops and ear drops.

Litigation
A class action was filed against Bayer AG on behalf of employees of the Brentwood Post Office in Washington, D.C., and workers at the U.S. Capitol, along with employees of American Media, Inc. in Florida and postal workers in general who alleged they suffered serious adverse effects from taking ciprofloxacin in the aftermath of the anthrax attacks in 2001. 
The action alleged Bayer failed to warn class members of the potential side effects of the drug, thereby violating the Pennsylvania Unfair Trade Practices and Consumer Protection Laws. 
The class action was defeated and the litigation abandoned by the plaintiffs.
A similar action was filed in 2003 in New Jersey by four New Jersey postal workers but was withdrawn for lack of grounds, as workers had been informed of the risks of ciprofloxacin when they were given the option of taking the drug.

Ciprofloxacin is an antibiotic. 
Ciprofloxacin belongs to a group of antibiotics called fluoroquinolones.

Ciprofloxacin is used to treat serious infections, or infections when other anitbiotics have not worked.

It's used to treat bacterial infections, such as:

chest infections (including pneumonia)
skin and bone infections
sexually transmitted infections (STIs)
conjunctivitis
eye infections
ear infections
Ciprofloxacin can be used to help stop people getting meningitis if they have been really close to someone with the infection.

Ciprofloxacin is only available on prescription.

Ciprofloxacin comes as tablets, a liquid that you drink, eardrops, eyedrops and an eye ointment. 
It's also given by injection, but this is usually done in hospital.

Ciprofloxacin tablets and liquid are not used as often as some other types of antibiotics because there's a risk of serious side effects.

Description    
Ciprofloxacin is a quinolone antibacterial related to recently marketed norfloxacin (10), ofloxacin (2), pefloxacin (2) and enoxacin. 
Ciprofloxacin has a broad spectrum of activity against gram-positive and gram-negative bacteria, and is useful in the treatment of urinary and upper respiratory tract infections.

Chemical Properties    
White Powder

Uses:
Ciprofloxacin is used in the treatment of infections from a wide range of aerobic gram-positive and aerobic gramnegative microorganisms. 
Ciprofloxacin has been shown to be effective against inhalational anthrax and reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis. 
Ciprofloxacin is also used in select respiratory infections, urinary tract infections, typhoid fever, some sexually transmitted diseases, and septicemia. 
Infectious diarrhea may be caused by organisms found in food or water and transferred by person-to-person contact. 
This may have a devastating effect, globally, especially in immunocompromised individuals. 
Ciprofloxacin is effective against those organisms that may contribute to infectious diarrhea, such as Escherichia coli (enterotoxigenic strains), Campylobacter jejuni, and select strains of Shigella; and is utilized when antibacterial therapy is medically indicated. 
Ciprofloxacin has also been utilized as a secondary agent in the treatment of tuberculosis.

Uses:
Fluorinated quinolone antibacterial

Definition    
ChEBI: A quinolone that is quinolin-4(1H)-one bearing cyclopropyl, carboxylic acid, fluoro and piperazin-1-yl substituents at positions 1, 3, 6 and 7, respectively.

Manufacturing Process    
Cyclopropyl-6-fluoro-4-oxo-7-(1-piperazinyl)-1,4-dihydro-3-quinolinecarboxylic acid was synthesized by heating of a mixture of 7-chloro-1-cyclopropyl-6- fluoro-1,4-dihydro-4-oxo-quinolin-3-carboxylic acid and 30.1 g dry piperazine in 100 ml DMSO for 2 hours at 135-140°C. 
DMSO was evaporated in high vacuum. 
The residue was heated with 100 ml of water, and was dried over CaCl2 in vacuum. 
Cyclopropyl-6-fluoro-4-oxo-7-(1-piperazinyl)-1,4-dihydro-3- quinolinecarboxylic acid obtained has a temperature of decomposition 255- 257°C.

Antimicrobial activity    
Ciprofloxacin exhibits potent activity against most Enterobacteriaceae, as well as against Acinetobacter spp. 
(MIC 0.25–1 mg/L), fastidious Gram-negative bacilli such as Mor. 
catarrhalis (MIC 0.06–0.25 mg/L) and Campylobacter jejuni(MIC 0.12 mg/L). 
In common with other quinolones, it is active against Bacillus anthracis. 
Ciprofloxacin is the most active quinolone against Ps. aeruginosa and exhibits good activity in vitro against other non-fermenting Gram-negative bacilli. 
In-vitro activity against Staph. aureus coagulase-negative staphylococci, Str. pyogenes, Str. pneumoniae and Enterococcus spp. (MIC c. 0.5–2 mg/L) is moderate. 
Most methicillin-resistant strains of staphylococci are resistant. 
Ciprofloxacin has poor activity against anaerobes, but is active against M. tuberculosis, Mycoplasma spp. and intracellular pathogens such as Chlamydia, Chlamydophila and Legionella.

Pharmaceutical Applications    
A 6-fluoro, 7-piperazinyl quinolone formulated as the hydrochloride for oral administration and as the lactate for intravenous use.

Pharmacokinetics    
Oral absorption: 50–80%
Cmax 500 mg oral: 1.5–2 mg/L after 1–2 h
200 mg intravenous (15-min infusion): 3.5 mg/L end infusion
Plasma half-life: 3–4 h
Volume ofdistribution: 3–4 L/kg
Plasma protein binding: 20–40%

Absorption
After escalating oral doses, mean peak plasma levels increase proportionately with dose.
However, accumulation occurs after repeated doses of 500 mg orally or 200 mg intravenously every 12 h： the apparent elimination half-life has been reported to rise to about 6 h after a regimen of 250 mg every 12 h for 6 days. 
Absorption is delayed, but seems unaffected by food and, in common with other quinolones, is reduced by certain antacids. 
Co-administration of sucralfate reduces the peak plasma concentrations to undetectable levels in many subjects (mean value from 2 to 0.2 mg/L) and the AUC is reduced to 12% of the value obtained when ciprofloxacin is administered alone. 
Ferrous sulfate and multivitamin preparations containing zinc significantly reduce absorption, which is also impaired in patients receiving cytotoxic chemotherapy for hematological malignancies. 
Calculated total bioavailability is 60–70%.
Distribution
Ciprofloxacin is widely distributed in body fluids, concentrations in most tissues and in phagocytic cells approximating those in plasma. 
Concentrations in the CSF, even in the presence of meningitis, are about half the simultaneous plasma levels.
Metabolism and excretion
Ciprofloxacin is partly metabolized to four metabolites, all but one of which (desethylciprofloxacin) display antibacterial activity. 
About 95% of a dose can be recovered from feces and urine. 
Around 40% of an oral and 75% of an intravenous dose appear in the urine over 24 h. 
Elimination is by both glomerular filtration and tubular secretion (60–70%) and is reduced by concurrently administered probenecid and by renal insufficiency. 
Ciprofloxacin is poorly removed by hemodialysis. 
Part of the administered drug is eliminated in the bile. 
An enterohepatic cycle results in prolongation of the half-life. 
The four metabolites are eliminated in the urine and feces at low concentration in comparison to the parent compound.

Chemical Synthesis    
Ciprofloxacin, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolincarboxylic acid (33.2.19), is synthesized in a completely analogous scheme, except that instead of using ethyl iodide in the alkylation stage, cyclopropyl bromide is used.

Ciprofloxacin is a second generation fluoroquinolone antibiotic that is widely used in the therapy of mild-to-moderate urinary and respiratory tract infections caused by susceptible organisms. 
Ciprofloxacin has been linked to rare but convincing instances of liver injury that can be severe and even fatal.

Ciprofloxacin is a quinolone that is quinolin-4(1H)-one bearing cyclopropyl, carboxylic acid, fluoro and piperazin-1-yl substituents at positions 1, 3, 6 and 7, respectively. 
Ciprofloxacin has a role as an antiinfective agent, a topoisomerase IV inhibitor, an antibacterial drug, an EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor, a DNA synthesis inhibitor, an antimicrobial agent, an environmental contaminant and a xenobiotic. 
Ciprofloxacin is a quinolone antibiotic, a fluoroquinolone antibiotic, a N-arylpiperazine, a quinolone, an aminoquinoline and a quinolinemonocarboxylic acid.

Ciprofloxacin is a synthetic broad spectrum fluoroquinolone antibiotic. 
Ciprofloxacin binds to and inhibits bacterial DNA gyrase, an enzyme essential for DNA replication. 
This agent is more active against Gram-negative bacteria than Gram-positive bacteria.

Methods of Manufacturing
Condensation of 2,4-dichloro-5-fluorobenzoylchloride with diethyl malonate by means of magnesium ethoxide in ether gives diethyl 2,4-dichloro-5-fluorobenzoylmalonate, which is partially hydrolyzed and decarboxylated with p-toluenesulfonic acid-water, yielding ethyl 2,4-dichloro-5-fluorobenzoylacetate. 
Condensation of this with triethylorthoformate in refluxing acetic anhydride affords ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-ethoxyacrylate, which is treated with cyclopropylamine in ethanol to give ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-cycloporpylaminoacrylate. 
Cyclization with NaH in refluxing dioxane then yields 7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, which is finally condensed with piperazine in hot DMSO to yield ciprofloxacin.

Uses:
This medication is used to treat a variety of bacterial infections. 
Ciprofloxacin belongs to a class of drugs called quinolone antibiotics. 
Ciprofloxacin works by stopping the growth of bacteria.
This antibiotic treats only bacterial infections. 
Ciprofloxacin will not work for virus infections (such as common cold, flu). 
Using any antibiotic when Ciprofloxacin is not needed can cause Ciprofloxacin to not work for future infections.

How to use Ciprofloxacin Tablet
Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start taking ciprofloxacin and each time you get a refill. 
If you have any questions, ask your doctor or pharmacist.

This medication may be taken with or without food as directed by your doctor, usually twice a day in the morning and evening.

Shake the container well for 15 seconds before pouring each dose. 
Carefully measure the dose using a special measuring device/spoon. 
Do not use a household spoon because you may not get the correct dose. 
Do not chew the contents of the suspension.

Do not use the suspension with feeding tubes because the suspension may clog the tube.

The dosage and length of treatment is based on your medical condition and response to treatment. 
Drink plenty of fluids while taking this medication unless your doctor tells you otherwise.

Take this medication at least 2 hours before or 6 hours after taking other products that may bind to it, decreasing its effectiveness. 
Ask your pharmacist about the other products you take. 
Some examples include: quinapril, sevelamer, sucralfate, vitamins/minerals (including iron and zinc supplements), and products containing magnesium, aluminum, or calcium (such as antacids, didanosine solution, calcium supplements).

Calcium-rich foods, including dairy products (such as milk, yogurt) or calcium-enriched juice, can also decrease the effect of this medication. 
Take this medication at least 2 hours before or 6 hours after eating calcium-rich foods, unless you are eating these foods as part of a larger meal that contains other (non-calcium-rich) foods. 
These other foods decrease the calcium binding effect.

Ask your doctor or pharmacist about safely using nutritional supplements/replacements with this medication.

For the best effect, take this antibiotic at evenly spaced times. 
To help you remember, take this medication at the same time(s) every day.

Continue to take this medication until the full prescribed amount is finished, even if symptoms disappear after a few days. 
Stopping the medication too early may result in a return of the infection.

IUPAC NAMES:
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)
1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid
1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic
1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid
1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-yl-quinoline-3-carboxylic acid
1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid
Ciprofloxacin

SYNONYMS:
1-cyclopropyl-6-fluoro-7-(1-piperazinyl)-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid
1-cyclopropyl-6-fluoro-4-oxo-7-(1-piperazinyl)-1,4-dihydro-3-quinolinecarbox
CIPROFLOXACIN USP 24
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic Acid, Bayq 3939,
CIPROFLOXACIN USP
CIPROFLOXACINBASE(PATENT-NOSUPPLY)
FLUOROQUINOLONECARBOXYLICACIDS
Ciprofloxacin BioChemika, ≥98.0% (HPLC)
CIPROFLOXACIN, MORPURE™
1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-yl-quinoline-3-carboxylic acid
Ciprofloxacin (base and/or unspecified salts)
ciprofloxacin hydrochloride/Ciflox/Ciproxan
Ciprofloxacin (200 mg)H0E3060.998mg/mg(ai)
Ciprofloxacin (200 mg)
Ciprooxacin (125 mg)
Bay 0 9867
Baycip
Cipmbay
Ciprinol
Cipro
Ciproxin
Flociprin：Septicide
Velmonit
1,4-Dihydro-1-cyclopropyl-6-fluoro-4-oxo-7-(1-piperazinyl)quinoline-3-carboxylic acid
1-Cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid
CPFX
PD-135305
1-Cyelopropyl-1，4-dihydro-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid
1-Cyclopropyl-6-fluoro-4-oxo-7-(1-piperazinyl)-1,4-dihydroquinoline-3-carboxylic Acid
3-quinolinecarboxylicacid,1,4-dihydro-1-cyclopropyl-6-fluoro-4-oxo-7-(1-piper
ciloxan
ciprobid
ciproiv
euciprin
CIPROBAY
CIPROFLOXACIN
CIPROFLOXACIN BASE
1-CYCLOPROPYL-6-FLUORO-1,4-DIHYDRO-4-OXO-7-(1-PIPERAZINYL)-3-QUINOLINECARBOXYLIC ACID
1-CYCLOPROPYL-6-FLUORO-4-OXO-7-PIPERAZIN-1-YL-1,4-DIHYDRO-QUINOLINE-3-CARBOXYLIC ACID
Ciprofloxacin (Cipro)
Ciflafin
Ciprine
Ciprobay 100
Ciprofloxacillin
3-Quinolinecarboxylic acid, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-
Enrofloxacin EP Impurity B
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid HCl
1-cyclopropyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid hydrochloride
3-Quinolinecarboxylic a
Clprofloxacin
Ciprofloxaicin USP
Enrofloxacin Impurity 2(Enrofloxacin EP Impurity B)
Ciproloxacin Solution, 1000ppm
Ciprof
1-cyclopropy-6-fluoro-4-oxo-7-(1-piperazin-4-iumyl)-3-quinolinecarboxylate
ciprofloxacin
85721-33-1
Ciprobay
Ciprofloxacine
Cipro
Ciproxan
Ciprofloxacina
Cipro IV
1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid
Ciprofloxacino
Ciprofloxacinum
Ciproflox
Ciproxina
BAY q 3939
Cetraxal
Ciloxan
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid
Cipro XR
Bay-09867
CPFX
1-Cyclopropyl-6-fluoro-4-oxo-7-(1-piperazinyl)-1,4-dihydro-3-quinolinecarboxylic aci
1-CYCLOPROPYL-6-FLUORO-4-OXO-7-PIPERAZIN-1-YL-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC ACID
3-Quinolinecarboxylic acid, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-
Ciprofloxacin (Cipro)
CHEMBL8
1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid
Ciprocinol
Cipromycin
Ciproquino
Bacquinor
Bernoflox
Cifloxin
Ciprinol
Ciprodar
Septicide
CHEBI:100241
Velmonit
Ciprofloxacin monohydrochloride
MFCD00185755
Ciprofloxacin, 98%
Ciprecu
Ciprogis
Ciprolin
Ciprolon
Ciprowin
Ciproxine
Citopcin
Corsacin
Fimoflox
Ipiflox
Italnik
Otiprio
Probiox
Proflaxin
Quinolid
Quintor
Roxytal
Spitacin
Superocin
Zumaflox
Baflox
Ciplus
Ciriax
Rancif
Cilab
Cixan
Cycin
Loxan
Unex
Sophixin Ofteno
Ciprobay UroAlcon Cilox
Bi-Cipro
Cipro (TN)
3-Quinolinecarboxylic acid, 1,4-dihydro-1-cyclopropyl-6-fluoro-4-oxo-7-(1-piperazinyl)-
Proksi 250
Proksi 500
Cyprobay
AuriPro
Eni
1-cyclopropyl-6-fluoro-4-oxo-7-piperazinylhydroquinoline-3-carboxylic acid
1-Cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-yl-1,4-dihydro-quinoline-3-carboxylic acid
1-cyclopropyl-6-fluoro-7-hexahydro-1-pyrazinyl-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid
BAY-o 9867
Ciprofloxacine [INN-French]
Ciprofloxacinum [INN-Latin]
1-Cyclopropyl-6-fluoro-7-(4-methyl-piperazin-1-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
Ciprofloxacino [INN-Spanish]
CIPRO IN DEXTROSE 5% IN PLASTIC CONTAINER
rubrum
Ciprine
Linhaliq
Bay 09867
CIPRO IN SODIUM CHLORIDE 0.9% IN PLASTIC CONTAINER
Ciprofloxacin,(S)
Ciprofloxacin [USAN:USP:INN:BAN]
Spectrum_000162
3-Quinolinecarboxylic acid, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-, hydrochloride
Prestwick0_000113
ANHYDROUS CIPROFLOXACIN
MLS001336035
Linhaliq [Liposomal Formulation]
ZINC20220
BAY O 9867 FREE BAS
BAY-O-9867 FREE BASE
Ciprofloxacin (JP17/USP/INN)
NINDS_000095
Ciprofloxacin, European Pharmacopoeia (EP) Reference Standard
Ciprofloxacin, United States Pharmacopeia (USP) Reference Standard
1-Cyclopropyl-6-fluoro-1,4-dihydro 4-oxo-7-[1-piperazinyl)-quinoline-3-carboxylic Acid
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl)-3-quinoline-carboxylic acid
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3- quinolinecarboxylic acid
1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline-carboxylic acid
1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline -3-carboxylic acid
1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylic acid
1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)quinoline-3-carboxylic acid
1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1piperazinyl)-3quinolinecarboxylic acid
1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(piperazin-1-yl)-quinoline-3-carboxylic acid
1-Cyclopropyl-6-fluoro-1,4-dihydro-7-(1-piperazinyl)-4-oxo-3-quinoline carboxylic acid
1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-4-ium-1-yl-quinoline-3-carboxylate;Ciprofloxacin
1-cyclopropyl-6-fluoro-7-(piperazin-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid
Ciprofloxacin, Pharmaceutical Secondary Standard; Certified Reference Material
1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-yl-1,4-dihydroquinoline-3-carboxylic acid hydrochloride