Ciprofloxacin

Absorption

A 250mg oral dose of ciprofloxacin reaches an average maximum concentration of 0.94mg/L in 0.81 hours with an average area under the curve of 1.013L/h*kg. The FDA reports an oral bioavailability of 70-80% while other studies report it to be approximately 60%. An early review of ciprofloxacin reported an oral bioavailability of 64-85% but recommends 70% for all practical uses.

Toxicity

Patients experiencing an overdose may present with nausea, vomiting, abdominal pain, crystalluria, nephrotoxicity, and oliguria. Ciprofloxacin overdose typically leads to acute renal failure. An overdose may progress over the next 6 days with rising serum creatinine and BUN, as well as anuria. Patients may require prednisone therapy, urgent hemodialysis, or supportive therapy. Depending on the degree of overdose, patients may recover normal kidney function or progress to chronic kidney failure.
The oral LD50 in rats is >2000mg/kg.
Ciprofloxacin for intratympanic injection or otic use has low systemic absorption and so it unlikely to be a risk in pregnancy or lactation. There is generally no harm to the fetus in animal studies, however high doses may lead to gastrointestinal disturbances in the mother which may increase the incidence of abortion. In human studies there was no increase in fetal malformations above background rates. The risk and benefit of ciprofloxacin should be weighed in pregnancy and breast feeding.
2/8 in vitro tests and 0/3 in vivo tests of mutagenicity of ciprofloxacin have yielded a positive result.
Oral doses of 200 and 300 times the maximum recommended clinical dose in rats and mice have shown no carcinogenicity or tumorigenicity.
Oral doses above the maximum recommended clinical dose have shown no effects on fertility in rats.

Description

Ciprofloxacin is a quinolone antibacterial related to recently marketed norfloxacin (10), ofloxacin (2), pefloxacin (2) and enoxacin. It 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.

Description

Ciprofloxacin, often called Cipro, its original trade name, is one of the world’s most widely prescribed antibiotics for bacterial infections. It is a member of the quinoline antibacterial class and is a descendant of norfloxacin, the first quinoline antibiotic to contain a fluorine atom.
In the 1980s, scientists at Bayer Pharmaceuticals discovered that replacing the ethyl group of norfloxacin with a cyclopropyl group greatly increased its Gram-negative bactericidal activity. In 1987, Bayer received US Food and Drug Administration approval for orally administered ciprofloxacin; the intravenous form was approved in 1991.
Since Bayer’s patent expired in 2004, ciprofloxacin has been widely distributed as an inexpensive broad-spectrum antibacterial. It is on the World Health Organization''s List of Essential Medicines.

The Uses of Ciprofloxacin

Ciprofloxacin is used in the treatment of infections from a wide range of aerobic gram-positive and aerobic gramnegative microorganisms. It has been shown to be effective against inhalational anthrax and reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis. It 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.

Indications

Ciprofloxacin is only indicated in infections caused by susceptible bacteria.
Ciprofloxacin immediate release tablets, oral suspensions, and intravenous injections are indicated for the treatment of skin and skin structure infections, bone and joint infections, complicated intra-abdominal infections, nosocomial pneumonia, febrile neutropenia, adults who have inhaled anthrax, plague, chronic bacterial prostatitis, lower respiratory tract infections including acute exacerbations of chronic bronchitis, urinary tract infections, complicated urinary tract infections in pediatrics, complicated pyelonephritis in pediatrics, and acute sinusitis.
A ciprofloxacin otic solution and otic suspension with hydrocortisone are indicated for acute otitis externa. Ciprofloxacin suspension with dexamethasone is indicated for acute otitis media in pediatric patients with tympanostomy tubes or acute otitis externa. A ciprofloxacin intratympanic injection is indicated for pediatric patients with bilateral otitis media with effusion who are having tympanostomy tubes placed or pediatric patients 6 months or older with acute otitis externa.
A ciprofloxacin eye drop is indicated for bacterial corneal ulcers and conjunctivitis. A ciprofloxacin eye ointment is indicated for bacterial conjunctivitis.
A ciprofloxacin extended release tablet is indicated for uncomplicated urinary tract infections, complicated urinary tract infections, and acute uncomplicated pyelonephritis.

Background

Ciprofloxacin is a second generation fluoroquinolone that has spawned many derivative antibiotics. It is formulated for oral, intravenous, intratympanic, ophthalmic, and otic administration for a number of bacterial infections.
The first ciprofloxacin containing product was FDA approved on 22 October 1987.

What are the applications of Application

Ciprofloxacin is a fluorinated quinolone antibacterial

Pharmacokinetics

Ciprofloxacin is a second generation fluoroquinolone that is active against many Gram negative and Gram positive bacteria. It produces its action through inhibition of bacterial DNA gyrase and topoisomerase IV. Ciprofloxacin binds to bacterial DNA gyrase with 100 times the affinity of mammalian DNA gyrase. There is no cross resistance between fluoroquinolones and other classes of antibiotics, so it may be of clinical value when other antibiotics are no longer effective. Ciprofloxain and its derivatives are also being investigated for its action against malaria, cancers, and AIDS.

Metabolism

Ciprofloxacin is primarily metabolized by CYP1A2. The primary metabolites oxociprofloxacin and sulociprofloxacin make up 3-8% of the total dose each. Ciprofloxacin is also converted to the minor metabolites desethylene ciprofloxacin and formylciprofloxacin. These 4 metabolites account for 15% of a total oral dose.
There is a lack of available data on the enzymes and types of reactions involved in forming these metabolites.