Fluoroquinolones. ATC code:
Pharmacology: Pharmacodynamics: Mechanism of action:
As a fluoroquinolone antibacterial agent, the bactericidal action of Ciprofloxacin results from the inhibition of both type II topoisomerase (DNA-gyrase) and topoisomerase IV, required for bacterial DNA replication, transcription, repair and recombination.
Spectrum of antibacterial activity:
Breakpoints separate susceptible strains from strains with intermediate susceptibility and the latter from resistant strains: See Table 1.
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Following an intravenous infusion of Ciprofloxacin the mean maximum serum concentrations were achieved at the end of infusion.
Pharmacokinetics of Ciprofloxacin were linear over the dose range up to 400 mg administered intravenously.
Comparison of the pharmacokinetic parameters for twice a day and three times a day intravenous dose regimen indicated no evidence of drug accumulation for Ciprofloxacin and its metabolites.
A 60-minute intravenous infusion of 200 mg Ciprofloxacin given every 12 hours, produced an equivalent area under the serum concentration time curve (AUC).
A 60-minute intravenous infusion of 400 mg Ciprofloxacin every 12 hours was bio-equivalent to a 500 mg oral dose every 12 hours with regard to AUC.
The 400 mg intravenous dose administered over 60 minutes every 12 hours resulted in a similar to that observed with a 750 mg oral dose.
A 60-minute infusion of 400 mg Ciprofloxacin every 8 hours is equivalent with respect to AUC to 750 mg oral regimen given every 12 hours.
Protein binding of Ciprofloxacin is low (20-30%). Ciprofloxacin is present in plasma largely in a non-ionised form and has a large steady state distribution volume of 2-3 L/kg body weight. Ciprofloxacin reaches high concentrations in a variety of tissues such as lung (epithelial fluid, alveolar macrophages, biopsy tissue), sinuses, inflamed lesions (cantharides blister fluid), and the urogenital tract (urine, prostate, endometrium) where total concentrations exceeding those of plasma concentrations are reached.
Low concentrations of four metabolites have been reported, which were identified as: Desethyleneciprofloxacin (M 1), Sulphociprofloxacin (M 2), Oxociprofloxacin (M 3) and Formylciprofloxacin (M 4). The metabolites display in-vitro antimicrobial activity but to a lower degree than the parent compound.
Ciprofloxacin is known to be a moderate inhibitor of the CYP 450 1A2 iso-enzymes.
Ciprofloxacin is largely excreted unchanged both renally and, to a smaller extent, facaelly.