Pharmacokinetics and peritoneal penetration of moxifloxacin in peritonitis
1 Pharma Research Centre Bayer AG, Wuppertal, Germany 2 Department of General Surgery, Leverkusen General Hospital Leverkusen, Germany
Received 3 April 2006; returned 15 May 2006; revised 21 June 2006; accepted 4 July 2006
*Corresponding author. Institute of Clinical Pharmacology, Bayer HealthCare AG, Aprather Weg, Building 470, D-42096 Wuppertal, Germany. Tel: +49-202-364289; Fax: +49-202-368180; E-mail: Heino.stass{at}bayerhealthcare.com
Objectives: To investigate the penetration of moxifloxacin into peritoneal exudate in patients with complicated intra-abdominal infections (cIAIs).
Patients and methods: Patients (n = 10) with evidence of peritonitis who required surgery with drainage of the abdominal cavity received a single intravenous infusion of moxifloxacin, 400 mg, over 1 h. Plasma and peritoneal exudate samples were obtained over 24 h, and moxifloxacin concentrations were measured by HPLC with fluorescence detection.
Results: Plasma moxifloxacin concentrations decreased from a geometric mean of 3.61 mg/L at 1 h to 0.36 mg/L at 24 h. Concentrations in peritoneal exudate were highest 2 h after the start of the infusion, reaching a geometric mean of 3.32 mg/L, and declined to a geometric mean of 0.69 mg/L at 24 h. The exudate/plasma concentration ratio rose from 1.45 at 2 h to 1.91 at 24 h; the 95% confidence intervals for the ratio excluded unity at all time points, suggesting that moxifloxacin penetrates and accumulates in peritoneal exudate. The area under the concentration–time curve (AUC) tended to be greater in exudate; the time to peak concentrations (Tmax) was longer in exudate than in plasma, as were half-life and mean residence time (MRT).
Conclusions: Following intravenous administration, moxifloxacin penetrated peritoneal exudate in patients with peritonitis, achieving and maintaining concentrations that exceed the MICs for pathogens commonly isolated in cIAIs. These findings support the clinical use of moxifloxacin as treatment for cIAIs.
Keywords: ascitic fluid , complicated intra-abdominal infections , peritoneal cavity , tissue distribution
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