Metronidazole kinetics and bioavailability in patients undergoing gastrointestinal surgery

Kinetics and bioavailability of metronidazole were studied in 17 patients admitted in our emergency care unit for gastrointestinal surgery. All were treated with intravenous metronidazole (500 mg three times a day) before, during, and for 4 days after surgery. Seven of the patients continued the intravenous regimen and seven were switched to oral therapy with the same dose and dosing interval for 4 additional days. Kinetic evaluations were performed at steady state on days 4 and 8. The main unexpected result was a consistent 51% increase in AUC with no increase in elimination t 1/2 when intravenous was changed to oral therapy. This change was accompanied by an upward 75% shift in the trough metronidazole plasma concentrations. There was no change when patients remained on intravenous metronidazole. Reduction of clearance on oral treatment appears to be the most likely explanation.