Design and trial of a metronidazole loading dose regimen for patients undergoing emergency surgery

A dosing regimen for administration of metronidazole to patients undergoing emergency surgery was designed using pharmacokinetic data. Computer estimates of the pharmacokinetic parameters from normal volunteers were used to determine a loading dose protocol that would achieve plasma metronidazole levels above 6.2 micrograms/mL, that is, above the minimum inhibitory concentration (MIC) of most pathogenic anaerobic bacteria, at the time of surgery. The protocol aimed to identify the minimum intravenous metronidazole dose in combination with a rectal suppository regimen. This was calculated to be a 1 g (two 500 mg) metronidazole rectal suppository dose administered when the decision to operate was made, followed by a 200 mg intravenous dose at the induction of anaesthesia if the time to surgery was within 1-8 h. This protocol was tested in 10 patients undergoing emergency abdominal/pelvic surgery. All patients in the trial were found to have levels well above the MIC at the time of surgery (mean = 17.06 micrograms/mL, s.d. = 4.76). It is concluded that appropriate use of metronidazole suppositories can minimize intravenous dosage requirements for metronidazole under conditions of emergency loading as well as elective surgery.