Pharmacokinetics of Ciprofloxacin in Healthy Volunteers after Oral and Intravenous Administration

Abstract

The pharmacokinetics of ciprofloxacin was studied in three groups of healthy volunteers comprising a total of 16 males and 16 females (age 21–35 years; body weight 52–80 kg). Single oral doses of 50,100, 250, 500 and 750 mg were given to fasting subjects. The 250 mg dose was repeated after a breakfast. Intravenous doses of 50, 100 and 200 mg were given by short infusion in a randomized cross-over sequence. Concentrations of the drug in serum and urine were determined by high-performance liquid chromatography and by a microbiological assay. Mean peak concentrations between 0.37 ± 0.49 mg/ I (100 mg dose) and 1.97 ± 0.50 (750 mg dose) were measured 60–75 min after oral administration. Twelve hours after 750 mg ciprofloxacin, serum concentrations were 0.15 ± 0.05 mg/1. Taking a breakfast reduced absorption by 15–20% compared to the fasting state, as judged by peak concentrations, AUC and renal excretion. After 200 mg i. v. (20 min infusion period), initial serum concentrations of 4.0 ± 1.2 mg/1 were observed which declined 12 h later to 0.070 ± 0.025 mg/1. Mean cumulated recovery of ciprofloxacin from urine over 24 h varied between 25.5% and 33.6% of oral doses and between 53.2% and 57.4% of intravenous doses. Two of the three metabolites seen in the chromatograms were identified as Ml and M3 (oxo-ciprofloxacin). Cumulated renal excretion after an oral 250 mg dose was 1.2 ± 0.4% of M1 and 5.5 ± 1.6% of M3. Bioavailability of oral doses varied from 0.64 ± 0.16 (100 mg) to 0.52 ± 0.11 (500 mg). The AUC was linearly proportional to a single dose of up to 250 mg. Ciprofloxacin was rapidly absorbed and distributed. High distribution volumes were calculated (mean VD_area 186–217 1). The terminal half-life (t_1/2ß ) was 3.1 to 5.4 h. Mean total body clearance was also high (600 to 693 ml/min 70 · kg)). Tolerance of ciprofloxacin was good for all oral doses and for intravenous administration up to 100 mg per dose. Intravenous infusion of 200 mg ciprofloxacin caused transient local irritation.