Pharmacokinetics of moxifloxacin in critically ill patients with impaired renal function undergoing pulse high-volume haemofiltration

Abstract

Moxifloxacin is an 8-methoxy quinolone with a broad spectrum of activity against clinically important pathogens. The aim of this study was to investigate the pharmacokinetics of intravenous (i.v.) moxifloxacin in critically ill patients with impaired renal function undergoing pulse high-volume haemofiltration (PHVHF) (n=8) to provide a reference for clinical rational moxifloxacin use in these patients. Blood and ultrafiltrate samples were obtained following i.v. infusion of a single 400 mg moxifloxacin dose. Concentrations of moxifloxacin in serum and ultrafiltrate were determined by HPLC analysis with fluorometric detection. Pharmacokinetics of moxifloxacin in plasma and ultrafiltrate were best described by a two-compartment model. Peak and trough serum moxifloxacin concentrations were 4.84 ± 1.85 mg/L and 1.17 ± 0.73 mg/L, respectively, at the arterial port after a single i.v. 400 mg dose. The mean elimination half-life was 4.82 ± 2.13 h, the volume of distribution was 82.63 ± 24.69 L and the calculated AUC(0-12) was 26.91 ± 10.96 mgh/L. Total clearance was 14.36 ± 8.44 L/h and the clearance of haemofiltration was 1.67 ± 0.95 L/h.C(max)/MIC(90) ratios and predicted AUC(0-24)/MIC(90) ratios were above the cut-off points for common pathogens that indicate clinical success. A single 400 mg i.v. dose of moxifloxacin is safe and efficacious in the treatment of critically ill patients infected with clinically common pathogens and impaired renal function undergoing PHVHF. It also should be kept in mind that the standard dose is not sufficient for this population infected with pathogens with a higher MIC(90) (0.5 mg/L).

Keywords: Critically ill patients; Moxifloxacin; Pharmacodynamics; Pharmacokinetics; Pulse high-volume haemofiltration.