Ciproted Mechanism of Action

Pharmacotherapeutic group: Fluoroquinolones.
Pharmacology: Pharmacodynamics: Mechanism of Action: As a fluoroquinolones 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.
PK/PD relationship: Efficacy mainly depends on the relation between the maximum concentration in serum (C_max) and the minimum inhibitory concentration (MIC) of ciprofloxacin for a bacterial pathogen and the relation between the area under the curve (AUC) and the MIC.
Mechanism of resistance: In-vitro resistance to ciprofloxacin can be acquired through a stepwise process by target site mutations in both DNA gyrase and topoisomerase IV. The degree of cross-resistance between ciprofloxacin and other fluoroquinolones that results is variable. Single mutations may not result in clinical resistance, but multiple mutations generally result in clinical resistance to many or all active substances within the class.
Impermeability and/or active substance efflux pump mechanisms of resistance may have a variable effect on the susceptibility to fluoroquinolones, which depends on physiochemical properties of the various active substances within the class and the affinity of transport systems for each active substance. All in-vitro mechanisms of resistance are commonly observed in clinical isolates. Resistance mechanisms that inactivate other antibiotics such as permeation barriers (common in Pseudomonas aeruginosa) and efflux mechanisms may affect susceptibility to ciprofloxacin.
Plasmid mediated resistance encoded by qnr-genes has been reported.
Pharmacokinetics: Ciprofloxacin is rapidly absorbed from the gastrointestinal tract. Oral bioavailability is approximately 70% and a peak plasma concentration of about 2.5 mcg 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 is not substantially affected overall. The plasma half-life is about 3.5 to 4.5 hours. Plasma protein binding ranges from 20 to 40%. Ciprofloxacin is eliminated by urinary excretion. Excretion is virtually complete within 24 hours; about 40 to 50% of an oral dose is excreted unchanged in the urine and about 15% as metabolites.