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Serum and tissue pharmacokinetics of intravenous metronidazole in surgical patients.

Intravenous administration of 1 g metronidazole during 30 min to 12 patients undergoing colorectal surgery yielded mean serum levels of 20.4 (+/- 4.9 SD) mg/l at 1 h, 15.6 (+/- 4.1) at 4 h and 3.9 (+/- 2.0) at 24 h after infusion. The mean elimination half-life of metronidazole was 8 h and the mean apparent volume of distribution 42 l. At 1-4 h after the infusion the median tissue/serum drug concentration ratio was 0.94 for rectus abdominis muscle and 0.76 for colonic mucosa. For adipose tissue the corresponding ratio was significantly lower (0.21, p less than 0.01) and highly unpredictable. Since in gastrointestinal surgery most wound infections develop in the cut surface of the abdominal fat, failure of metronidazole to reach bactericidal concentrations in adipose tissue could be a risk factor in this respect, contributing to the variable reported results of metronidazole prophylaxis.