Pharmacokinetics of moxifloxacin in patients with severe sepsis or septic shock

To investigate the steady-state pharmacokinetics of moxifloxacin in critically ill patients after intravenous administration of the 400 mg fixed dose. Fifteen adult patients with severe sepsis (n = 3) or septic shock (n = 12) were enrolled in this dual-centre, prospective, open-label study. Moxifloxacin was administered with the recommended dose of 400 mg once daily i.v. for at least 5 days. Blood samples were obtained before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18 and 24 h after the third administration. Moxifloxacin concentrations in plasma were measured by HPLC with fluorescence detection. Data for 400 mg moxifloxacin i.v. were as follows (geometric mean): C (max): 3.5 mg/l, t (A1/2): 7.8 h and AUC (48-72 h): 25 mg h/l. In five individual patients AUC (48-72 h) was < 20 mg h/l. The main pharmacokinetics/pharmacodynamics parameter predicting clinical efficacy of moxifloxacin is AUC/MIC. The mean AUC of patients with severe sepsis or septic shock was lower compared to healthy volunteers (39 mg h/l). In 5 of 12 patients the AUC was halved compared to healthy volunteers.