Ciprofloxacin

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Ciprofloxacin
Systematic (IUPAC) name
1-cyclopropyl-6-fluoro-4-oxo-
7-piperazin-1-yl-quinoline-3-carboxylic acid
Identifiers
CAS number 85721-33-1
ATC code J01MA02 S01AX13 S03AA07
PubChem 2764
DrugBank APRD00424
Chemical data
Formula C17H18FN3O3 
Mol. mass 331.346
Pharmacokinetic data
Bioavailability 69%[1]
Metabolism Hepatic, including CYP1A2
Half life 4 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

B3 (Australia), C (USA)
Legal status

Schedule 4 (Australia)
Prescription Only (UK)
Routes Oral, intravenous, topical (ear drops, eye drops)

Ciprofloxacin is the generic international name for the synthetic antibiotic manufactured and sold by Bayer Pharmaceutical under the brand names Cipro®, Ciproxin® and Ciprobay® (and other brand names in other markets, e.g. veterinary drugs), belonging to a group called fluoroquinolones. Ciprofloxacin is bactericidal. Its mode of action depends upon blocking bacterial DNA replication by binding itself to an enzyme called DNA gyrase, thereby causing double-stranded breaks in the bacterial choromosome.

Contents

[edit] Activity

Ciprofloxacin is a broad-spectrum antibiotic that is active against both Gram-positive and Gram-negative bacteria. It functions by inhibiting topoisomerase, an enzyme necessary to separate replicated DNA, thereby inhibiting cell division.

Weak activity against:

No activity against:

  • and others

The major adverse effect seen with use is gastrointestinal irritation, common with many antibiotics. Because of its general safety, potency and broad spectrum activity, ciprofloxacin was initially reserved as a drug of last resort for use on difficult and antibiotic-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.

In cell culture it is used to treat infection with mycoplasma.

[edit] Label information

The drug is available for oral, parenteral and topical 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. Ciprofloxacin is also known to cause swelling of certain joints and cartilage.

[edit] 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 entirely clear.[2]

[edit] Contraindications

Metal cations such as aluminium, magnesium, calcium, ferrous sulphate, and zinc are thought to form chelation complexes with fluoroquinolone antibiotics and prevent the drugs from being absorbed. Because of this, avoid taking ciprofloxacin with antacids which contain aluminium, magnesium or calcium. 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. Achilles tendon rupture due to ciprofloxacin use is typically associated with renal failure.

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]

Fluoroquinolones are increasingly contraindicated for patients who have been to S.E. Asia due to the growing prevalence of antibiotic resistance to the class of antibiotics in that region.[6]

[edit] Dosing

Ciprofloxacin is available in oral tablets (250, 500, 750, and 1000 mg), as well as ready-made infusion bottles (200 and 400 mg). A combination preparation of ciprofloxacin 500 mg and tinidazole 600 mg is marketed under the name Ciplox-TZ® for infections where anaerobes or protozoa together with ciprofloxacin-sensitive aerobes are likely.

Due to its elimination half-life, ciprofloxacin is administered twice daily. No dose adjustments are generally required for mild to moderate renal impairment.

Cipro® brand ciprofloxacin 500mg tablets
Cipro® brand ciprofloxacin 500mg tablets

[edit] 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 expiry of its patent rights to ciprofloxacin in the early 2000s and the predictable loss of market share to generic ciprofloxacin, Bayer has resorted to the usual strategy of pharmaceutical companies in such a situation; 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 2001 anthrax attacks after the destruction of the World Trade Center.

Generic ciprofloxacin is now available in many markets around the world including the USA. In addition two new once daily formulations have been launched in the USA. Bayer have marketed Cipro XR® which is an extended release formulation. Meanwhile Depomed have developed ProQuin XR® another once daily formulation of ciprofloxacin which uses a gastric retention polymer technology to slow the release of ciprofloxacin into the blood.

[edit] Footnotes

  1. ^ 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.
  2. ^ 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.
  3. ^ Spivey JM, Cummings DM, Pierson NR. Failure of prostatitis treatment secondary to probable ciprofloxacin-sucralfate drug interaction. Pharmacotherapy 1996;16:314-6. PMID 8820479.
  4. ^ Drug effects of Ciprofloxacin
  5. ^ Brouwers JR. Drug interactions with quinolone antibacterials. Drug Saf 1992;7:268-81. PMID 1524699.
  6. ^ Fluoroquinolone Resistance in Neisseria gonorrhoeae -- Colorado and Washington, 1995 [1]

[edit] External links

v • d • e
Quinolones (J01M)
Fluoroquinolones Ciprofloxacin, Enoxacin, Fleroxacin, Gatifloxacin, Gemifloxacin, Grepafloxacin, Levofloxacin, Lomefloxacin, Moxifloxacin, Norfloxacin, Ofloxacin, Pefloxacin, Prulifloxacin, Rufloxacin, Sparfloxacin, Temafloxacin, Trovafloxacin, Sitafloxacin
Other quinolones Cinoxacin, Flumequine, Nalidixic acid, Oxolinic acid, Pipemidic acid, Piromidic acid, Rosoxacin
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