title: Inappropriate use of metronidazole in gastrointestinal surgery.
abstract: Pharmacokinetic data suggest that current treatment regimens of metronidazole in abdominal surgery are not always appropriate. We have examined antibiotic concentrations during emergency and elective surgery using a specific and sensitive high pressure liquid chromatography assay. Serum and tissue concentrations were measured after intravenous infusion during intra-abdominal surgery and after suppositories given before appendicectomy. After intravenous dosage, bactericidal concentrations were reached in serum (13.6 +/- 7.8 micrograms/ml), bowel (9.0 +/- 6.6 micrograms/g), tumour (9.9 +/- 7.1 micrograms/g) and subcutaneous fat (4.9 +/- 3.2 micrograms/g). After suppositories the concentrations were: serum 4.6 +/- 2.7 micrograms/ml, appendix 1.1 +/- 0.6 micrograms/g, fat 1.5 +/- 0.9 micrograms/g and peritoneal fluid 4.7 +/- 4.3 micrograms/g. These values were obtained at a mean interval of 86.9 +/- 27.5 min following administration of the drug. Serum concentrations were measured during post-surgical infusion of 500 mg i.v. 8 or 12 hourly. Mean concentrations after 8 hourly doses were 16.3 +/- 4.85 micrograms/ml pre-dose and 28.7 +/- 6.76 micrograms/ml post-dose, with evidence of drug accumulation by detection of metabolites. Twelve hourly infusions gave pre-dose levels of 7.4 +/- 3.86 micrograms/ml and post-dose levels of 17.1 +/- 3.69 micrograms/ml. Metronidazole (500 mg) intravenously at induction of anaesthetic gives effective prophylactic concentrations in all tissues including tumour, but a metronidazole 1 g suppository before appendicectomy does not provide reliable tissue concentrations. Metronidazole (500 mg) i.v. 12 hourly gives effective bactericidal concentrations of the drug and is more economical.
authors.affiliation: Department of Surgery, St James's University Hospital, Leeds, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Ingoldby
authors.forename: P H
authors.initials: PH
authors.lastname: Dean
authors.forename: P
authors.initials: P
authors.lastname: Vowden
authors.forename: G R
authors.initials: GR
authors.lastname: Giles
mesh_terms: D000368:Aged; D001062:Appendectomy; D001770:Blood Bactericidal Activity; D002851:Chromatography, High Pressure Liquid; D013505:Digestive System Surgical Procedures; D006801:Humans; D007262:Infusions, Intravenous; D007432:Intraoperative Period; D008795:Metronidazole / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D011292:Premedication; D013056:Spectrophotometry, Ultraviolet
chemical_list: D008795:Metronidazole