Ciprofloxacin 1,4-dihydro-1-cyclopropyl-6-fluoro- 4-oxo-7-(1-piperazinyl)- 3-quinolinecarboxylic acid CAS number 85721-33-1 ATC code J01MA02, S01AX13, S03AA07 Chemical formula C17H18FN3O3 Molecular weight 331.345 Bioavailability 69%[1] Metabolism Hepatic, including CYP1A2 Elimination half-life 4 hours Excretion Renal Pregnancy category B3 (Australia) Legal status Schedule 4 (Australia) Routes of administration Oral, topical (ear drops, eye drops) Ciprofloxacin is the generic international name for the synthetic antibiotic manufactured and sold by Bayer Pharmaceutical under the brand name Cipro® (and other brand names in other markets, e.g. veterinary drugs), belonging to a group called fluoroquinolones. Ciprofloxacin is bactericidal and its mode of action depends on blocking of bacterial DNA replication by binding itself to an enzyme called DNA gyrase, which allows the untwisting required to replicate one DNA double helix into two. Notably the drug has 100 times higher affinity for bacterial DNA gyrase than for mammalian. Contents 1 Activity 2 Label information 3 Interactions 4 Contraindications 5 Business aspects 6 References 7 Links Activity Ciprofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. Enterobacteriaceae Vibrio Hemophilus influenzae Neisseria gonorrhoeae Neisseria menigitidis Moraxella catarrhalis Brucella Campylobacter Mycobacterium intracellulare Legionella sp. Pseudomonas aeruginosa Bacillus anthracis - that causes anthrax Weak activity against: Streptococcus pneumoniae Chlamydia trachomatis Chlamydia pneumoniae No activity against: Bacteroides Burkholderia cepacia Enterococcus faecium Ureaplasma urealyticum and others The major adverse effect seen with use of is gastrointestinal irritation, common with many antibiotics. Because of its general safety, potency and broad spectrum activity, ciprofloxacin was initially reserved as a "last-resort" drug for use on difficult and drug-resistant infections. As with any antibiotic, however, increasing time and usage has led to an increase in ciprofloxacin-resistant infections, mainly in the hospital setting. Also implicated in the rise of resistant bacteria is the use of lower-cost, less potent fluoroquinolones, and the widespread addition of ciprofloxacin and other antibiotics to the feed of farm animals, which leads to greater and more rapid weight gain, for reasons which are not clear. Label information The drug is available for oral and parenteral use. It is used in lower respiratory infections (pneumonias), urinary tract infections, STDs, septicemias, Legionellosis and atypical Mycobacterioses. Dosage in respiratory infections is 500-1500 mg a day in 2 doses. It is contraindicated in children, pregnancy, and in patients with epilepsy. Dose adjustment or avoidance may be necessary with liver or renal failure. Ciprofloxacin can cause photosensitivity reactions and can elevate plasma theophylline levels to toxic values. It can also cause constipation and sensitivity to caffeine. Interactions Quercetin, a flavonoid occasionally used as a dietary supplement may interact with fluroquinolones, as quercetin competitively binds to bacterial DNA gyrase. Some foods such as garlic and apples contain high levels of quercetin. Whether this inhibits or enhances the effect of Fluoroquinolones is not immediately clear[2]. Contraindications Metal cations such as aluminium, magnesium, calcium, ferrous sulfate, and zinc are thought to form chelation complexes with fluoroquinolone antibiotics and prevent the drugs from being absorbed. Because of this, avoid taking antacids which contain aluminium, magnesium or calcium with ciprofloxacin. Sucralfate, which has a high aluminium content, also reduces the bioavailability of ciprofloxacin to approximately 4%[3]. Ciprofloxacin may be taken with meals or on an empty stomach. Ciprofloxacin should NOT be taken with dairy products or calcium-fortified juices alone, but may be taken with a meal that contains these products[4]. Heavy exercise is discouraged, as achilles tendon rupture has been reported in patients taking ciprofloxacin. The toxicity of drugs that are metabolised by the cytochrome P450 system is enhanced by concomitant use of some quinolones. They may also interact with the GABA A receptor and cause neurological symptoms; this is further augmented by certain non-steroidal anti-inflammatory drugs[5]. Business aspects The discovery and development of ciprofloxacin is that rare case of an actual groundbreaking new drug development, opening up an entire new class of antibiotics for further research, development, and marketing. Even more remarkable, it seems to be a case where the first drug discovered of this class remains the 'gold standard' in terms of efficacy, with the other drugs developed by other pharmaceutical companies relegated to 'me-too' status and forced to compete on the basis of lower cost. Encouraged by the magnitude of this success, as well as the influx of cash, Bayer Pharmaceutical embarked on a plan to remake itself from a minor pharmaceutical manufacturer into a major player in the international pharmaceutical business, with a lock on the antibiotic field. Unfortunately, a combination of the tendency for antibiotics to be viewed as a commodity and prescribed on the basis of lowest cost, Bayer's inability to follow up with another 'blockbuster' discovery, and a general downturn in the international pharmaceutical business forced Bayer into a major downsizing in 2000-2001. Faced with the imminent expiration of its patent rights to ciprofloxacin in the early 2000's and the predictable loss of market share to generic ciprofloxacin, Bayer has resorted to the usual strategy of pharmaceutical companies in such a situaton; focus on the development and patenting of new variations of the old drug (i.e. pediatric ciprofloxacin, intravenous ciprofloxacin, once-a-day ciprofloxacin, etc.), which will have the side effect of extending the patent on the original drug. "Cipro" became a household word during the anthrax mail attacks after the destruction of the World Trade Center. Unfortunately, Bayer not only took a severe financial blow from the costs involved in rapidly increasing production of the drug to be sold to the government at far below market price. References ^  Drusano GL, Standiford HC, Plaisance K, Forrest A, Leslie J, Caldwell J. Absolute oral bioavailability of ciprofloxacin. Antimicrob Agents Chemother 1986;30:444-6. PMID 3777908. ^  Hilliard JJ, Krause HM, Bernstein JI, Fernandez JA, Nguyen V, Ohemeng KA, Barrett JF. 'A comparison of active site binding of 4-quinolones and novel flavone gyrase inhibitors to DNA gyrase. Adv Exp Med Biol. 1995;390:59-69. PMID 8718602. ^  Spivey JM, Cummings DM, Pierson NR. Failure of prostatitis treatment secondary to probable ciprofloxacin-sucralfate drug interaction. Pharmacotherapy 1996;16:314-6. PMID 8820479. ^  Brouwers JR. Drug interactions with quinolone antibacterials. Drug Saf 1992;7:268-81. PMID 1524699. Links Data sheet for Cipro Fluoroquinolone Toxicity Research Foundation querying the overall safety of fluoroquinolones Emergency Medicine Magzine a review of ciprofloxacin in relation to other fluoroquinolonesde:Ciprofloxacin Search Term: "Ciprofloxacin" Categories: Fluoroquinolone antibiotics