Bioavailability of ciprofloxacin after multiple enteral and intravenous doses in ICU patients with severe gram-negative intra-abdominal infections

Background: Few data are available on the pharmacokinetics of multiple enteral dosing of ciprofloxacin in critically ill intensive care patients and none for those with severe gram-negative intra-abdominal infections (GNIAI). Objective: To determine the bioavailability of enteral ciprofloxacin in tube-fed intensive care patients with severe GNIAI. Design: A randomized crossover study. Setting: University-based medical center. Patients: 5 critically ill intensive care patients with GNIAI and an estimated creatinine clearance > 25 ml/min who received continuous tube feeding. Interventions: Multiple doses of enteral 750 mg b.i.d. versus 400 mg b.i.d.i.v. ciprofloxacin. Measurements: The calculated 12-h area under the serum concentration versus time curve after 750 mg b.i.d. enteral dosing was equivalent to that after 400 mg b.i.d.i.v. The mean bioavailability of enteral dosing was 53.1% [95% confidence interval (CI) 43.5-62.8]. In seven additional patients, the mean serum steady-state concentration at 2 h after enteral administration was 3.9 μg/ml (95% CI 1.9-5.9), not significantly different from that found in the crossover study (p = 0.4). Conclusions: In tube-fed intensive care patients with severe GNIAI, the bioavailability of enteral ciprofloxacin is adequate.