Pharmacokinetics of ciprofloxacin during continuous renal replacement therapy in intensive care patients - new assessment

Background: The first studies on the pharmacokinetics of ciprofloxacin during continuous renal replacement therapy were conducted using filters with a relatively small surface area and with lower intensity of the procedure than nowadays. The aim of this study was to assess the pharmacokinetics and the probability of achieving pharmacokinetic/pharmacodynamic (PK/PD) target for ciprofloxacin during renal replacement therapy using a filter with large surface area and higher intensity. Methods: Eighteen patients were considered eligible for treatment with ciprofloxacin (400 mg every eight hours intravenously) during continuous renal replacement therapy. Blood samples were collected from the arterial line of the renal replacement circuit before (time 0) and after 30, 60, 75, 90, 120, 180, 240, and 480 minutes following the initiation of ciprofloxacin infusion. Ciprofloxacin concentrations in the collected samples were determined using fully validated liquid chromatography. The pharmacokinetic analysis was performed using non-compartmental analysis. The measure adopted to assess the efficacy of the antibiotic therapy was the proportion of patients for whom pre-defined PK/PD indices were achieved. Results: There was a considerable inter-individual variability observed in pharmacokinetic parameters for ciprofloxacin. 100% of patients achieved PK/PD target AUC0(-24)/MIC > 40, AUC0(-24)/MIC > 125, AUC0(-24)/MIC > 250 for MIC 1, 0.25, and 0.125 mu g mL(-1), respectively. Conclusions: High doses of ciprofloxacin (400 mg every eight hours intravenously) during continuous renal replacement therapy should be used to maximally increase the proportion of patients in whom clinical efficacy, expressed as achieving the PK/PD target, is reached.