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/l (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/l. 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/l were observed which declined 12 h later to 0.070 +/- 0.025 mg/l. 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 M1 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.(ABSTRACT TRUNCATED AT 250 WORDS)