An overview of the pharmacology of intravenously administered ciprofloxacin.

Ciprofloxacin is a new quinolone carboxylic acid with a broad spectrum of activity against common nosocomial pathogens. Intravenous infusions of 200 mg over one-half hour result in peak serum concentrations of 3.80 +/- 0.62 micrograms/ml. Dose-ranging studies have revealed a linear increase in the area under the concentration-time curve in the range from 25 to 200 mg. The terminal elimination half-life is four to five hours in normal subjects. Serum clearance in normal subjects averages 23.7 +/- 5.1 liters/hour/1.73 m2, with renal clearance accounting for 66.6 +/- 11.0 percent of the total serum clearance. The renal clearance is far in excess of the glomerular filtration rate, and administration of probenecid decreases the observed renal clearance. Hence, net tubular secretion contributes to renal clearance. There are four metabolites of ciprofloxacin, some with microbiologic activity: desethyl-ciprofloxacin (M1), sulfo-ciprofloxacin (M2), oxo-ciprofloxacin (M3), and formyl-ciprofloxacin (M4). Ciprofloxacin is excreted into bile as the parent compound. Administration of radiolabeled ciprofloxacin has revealed that 74.9 percent was recovered in the urine, as parent compound plus metabolites, with 14 percent of the radiolabel recovered in the feces. Multiple-dosing studies carried out with doses ranging from 25 to 200 mg administered twice daily for a week have shown rapid attainment of steady state and no accumulation. Renal dysfunction causes a decrease in serum clearance, with anephric volunteers having a clearance approximately 50 percent of that of normal subjects. A maximal dose reduction of 50 percent should be initiated when creatinine clearance is reduced to 20 to 30 ml/minute/1.73 m2. Because of the variability in the drug's terminal half-life in patients with renal impairment, the reduced dose should be given on an every-12-hour schedule.