Clinical pharmacokinetics of ciprofloxacin in patients with major burns

Objective: To better master the use of ciprofloxacin (CPF) in burn patients, a clinical study, including pharmacokinetics in serum and urine, was undertaken in a pathophysiologically homogeneous population of major-burn subjects. Methods: Twelve major-burn patients who were infected with Pseudomonas aeruginosa, enterobacteria and gram-positive cocci, received CPF (600 mg t.i.d.). The mean body surface area affected by third-degree burns was 31.8 ± 14.5%. Two series of blood samples were drawn after the first and seventh doses; urine was collected during the first infusion. Levels of CPF in serum and urine were measured by means of high-performance liquid chromatography. A non-compartmental method was used for kinetic and graphic analysis of concentration–time pairs. Results: No adverse effects were noted. Trough concentrations measured on day 3 (mean ± SD) were above the minimum inhibitory concentration (MIC) for the organism responsible for infection; i.e., 2.0 ± 1.2 μg · ml⁻¹, and maximum concentrations were high 9.9 ± 3.4 μg · ml⁻¹. An area under the concentration–time curve (AUC)/MIC ratio above 125 SIT⁻¹ (where SIT is the serum inhibitory titer), which has been strongly correlated with clinical response and time to bacterial eradication, was achieved in 11 patients with a MIC of 0.5 μg · ml⁻¹. There was a statistically significant difference between C_min and AUC determined on day 1 and day 3. In contrast to healthy volunteers, CPF clearance rates were notably decreased. Conclusion: The pharmacokinetics of CPF was altered in major-burn patients. The recommended dosage regimen for administration of CPF, i.e. 600 mg t.i.d. shows no adverse effects and a good microbiological efficacy. Received: 13 October 1998 / Accepted in revised form: 8 June 1999