We aimed to investigate the pharmacokinetics of
fosfomycin and
metronidazole after intraperitoneal administration of the combination of
fosfomycin and
metronidazole in patients undergoing laparoscopic
appendectomy for uncomplicated
appendicitis. We included eight otherwise healthy men undergoing laparoscopic
appendectomy. The trial treatment was administered at the end of the
surgical procedure and left in the abdominal cavity. Trial drugs consisted of 4 g
fosfomycin and 1 g
metronidazole in a total volume of 500.2 mL. Blood samples were collected prior to and ½, 1, 2, 4, 8, 12 and 24 h after administration. High-performance liquid chromatography-mass spectrometry was used for the measurement of plasma concentrations, and pharmacokinetic calculations were undertaken. Antimicrobial susceptibility testing was undertaken on isolates from intraoperatively collected specimens. The median maximal concentration for
fosfomycin in plasma was 104.4 mg/L, median time point for the maximal concentration was 1.5 h, median half-life 3.0 h, and median area under the curve 608 mg*h/L. The median maximal concentration for
metronidazole in plasma was 13.6 mg/L, median time point for the maximal concentration was 2.0 h, median half-life 7.3 h, and median area under the curve was 164 mg*h/L. All aerobic bacteria were susceptible to
fosfomycin, and all anaerobes were susceptible to
metronidazole. Plasma concentrations of
fosfomycin and
metronidazole were in line with concentrations reported from pharmacokinetic studies after
intravenous administration and were within therapeutic ranges.