Steady-state pharmacokinetics of ciprofloxacin in plasma from patients with nosocomial pneumonia: penetration of the bronchial mucosa

Abstract

A 30-min intravenous (i.v.) infusion of 200 mg of ciprofloxacin was administered twice daily to 12 patients with nosocomial pneumonia scheduled to undergo diagnostic fiberoptic bronchoscopy. The pharmacokinetics of ciprofloxacin were examined at the presumed steady state after 5 days of treatment. Eleven successive plasma samples were collected in the interval from 0 to 12 h after administration, and bronchial mucosa samples were taken 2 h after administration. Concentrations of drug in all samples were assayed by high-performance liquid chromatography with fluorimetric detection. The results showed that the kinetics in plasma did not differ from those determined previously in healthy volunteers. The mean concentrations in plasma peaked at 4.94 +/- 2.90 mg/liter at the end of infusion. The terminal half-life was 4.95 +/- 2.81 h, and the mean residence time 6.13 +/- 3.17 h. A large volume of distribution was calculated: 2.59 +/- 1.43 liters/kg. Mean total body clearance was 23.3 +/- 10.1 liters/h. The concentrations in bronchial mucosa reached 21.6 +/- 5.63 micrograms/g 2 h after drug intake. The tissue-versus-plasma concentration ratios ranged from 10.1 to 26.3 (mean value, 16.9 +/- 5.43). After 6 to 12 days of i.v. treatment, four patients were switched to oral ciprofloxacin. We propose a model for the simultaneous fit of the concentration-time curves obtained after i.v. infusion and oral dosing. The concentrations in tissue observed in this study were in excess of the MICs for bacteria considered to be susceptible to ciprofloxacin.