Repeated determination of moxifloxacin concentrations in interstitial space fluid of muscle and subcutis in septic patients

BACKGROUND: For an effective antimicrobial treatment, it is crucial that antibiotics reach sufficient concentrations in plasma and tissue. Currently no data exist regarding moxifloxacin plasma concentrations and exposure levels in tissue under septic conditions. OBJECTIVES: To determine the pharmacokinetics of moxifloxacin in plasma and interstitial space fluid over a prolonged period. PATIENTS AND METHODS: Ten septic patients were treated with 400 mg of moxifloxacin once a day; on days 1, 3 and 5 of treatment plasma sampling and microdialysis in the subcutis and muscle of the upper thigh were performed to determine concentrations of moxifloxacin in different compartments. This trial was registered in the German Clinical Trials Register (DRKS, register number DRKS00012985). RESULTS: Mean unbound fraction of moxifloxacin in plasma was 85.5 ± 3.4%. On day 1, Cmax in subcutis and muscle was 2.8 ± 1.8 and 2.5 ± 1.3 mg/L, respectively, AUC was 24.8 ± 15.1 and 21.3 ± 10.5 mg·h/L, respectively, and fAUC0-24/MIC was 100.9 ± 62.9 and 86.5  ±  38.3 h, respectively. Cmax for unbound moxifloxacin in plasma was 3.5 ± 0.9 mg/L, AUC was 23.5 ± 7.5 mg·h/L and fAUC0-24/MIC was 91.6 ± 24.8 h. Key pharmacokinetic parameters on days 3 and 5 showed no significant differences. Clearance was higher than in healthy adults, but tissue concentrations were comparable, most likely due to a lower protein binding. CONCLUSIONS: Surprisingly, the first dose already achieved exposure comparable to steady-state conditions. The approved daily dose of 400 mg was adequate in our patient population. Thus, it seems that in septic patients a loading dose on the first day of treatment with moxifloxacin is not required.