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Pharmacology: Pharmacodynamics: Mechanism of Action: Ciprofloxacin is bactericidal and kills bacteria rapidly. It acts via inhibition of bacterial DNA gyrase, it also inhibits bacterial topoisomerase IV, ultimately resulting in interference with DNA function. Ciprofloxacin is highly active against a wide range of Gram-positive and Gram-negative organisms and has shown activity against some anaerobes, Chlamydia spp. and Mycoplasma spp. Killing curves demonstrate the rapid bactericidal effect against sensitive organisms and it is often found that minimum bactericidal concentrations are in the range of minimum inhibitory concentrations. Ciprofloxacin has been shown to have no activity against Treponema pallidum and Ureaplasma urealyticum. Nocardia asteroides and Enterococcus faecium are resistant.
Pharmacokinetics: Ciprofloxacin is rapidly and well-absorbed from the gastrointestinal tract. Oral bioavailability is approximately 70% and a peak plasma concentration of about 2.5 μg per mL is achieved 1 to 2 hours after a dose of 500 mg by mouth. Absorption may be delayed by the presence of food, but it is not substantially affected overall. The plasma half-life is about 3.5 to 4.5 hours and there is evidence of modest accumulation. Half-life may be prolonged in severe renal failure a value of 8 hours has been reported in end-stage renal disease and to some extent in the elderly. There is limited information on the effect of liver dysfunction; in one study the half-life of Ciprofloxacin was slightly prolonged in patients with severe cirrhosis of the liver. With one or two exceptions, most studies have shown the pharmacokinetics of Ciprofloxacin to be not markedly affected by cystic fibrosis.
Plasma protein-binding ranges from 20 to 40%. Ciprofloxacin is widely distributed in the body and tissue penetration is generally good. It appears in the CSF, but concentrations are only about 10% of those in plasma when the meninges are not inflamed.
Ciprofloxacin is eliminated principally by urinary excretion, but non-renal clearance may account for about a third elimination and includes hepatic metabolism, biliary excretion and possibly transluminal secretion across the intestinal mucosa. At least 4 active metabolites have been identified. Oxociprofloxacin appears to be the major urinary metabolite and sulphociprofloxacin the primary faecal metabolite. Urinary excretion is by active tubular secretion as well as glomerular filtration and is reduced by probenecid; it is virtually complete within 24 hours. About 40-50% of an oral dose is excreted unchanged in the urine and about 15% as metabolites. Up to 70% of a parenteral dose may be excreted unchanged within 24 hours and 10% as metabolites. Faecal excretion over 5 days has accounted for 20-35% of an oral dose and 15% of an intravenous dose.
