Tissue diffusion of metronidazole according to two routes of administration : intravenous and rectal

The diffusion of metronidazole, administred in antibiotic prophylaxis of colorectal surgery, in the epiploic fat, for a dose of 500 mg, was studied according to two routes of administration, intravenous or rectal. Eighteen patients are included in the group IV and 16 patients in the suppository group. Plasma and tissue concentrations were determined by HPLC. Plasma concentrations were compared during the operation, we note that they are inferior about 50 % for the administration by suppository in comparaison with the IV route. After IV administration, the means of plasma and tissue concentrations are 18.9 ± 6.0 µg.ml- 1 and 2.9 ± 1.4 µg.g- 1 at the skin incision, and decrease to 9.4 ± 2.0 µg.ml- 1 and 2.8 ± 1.0 µg.g- 1 after 2 hours. In the same period of time, plasma and tissue concentrations obtained after rectal administration are 7.1 ± 4.0 µg.ml- 1 and 1.5 ± 0.8 µg.g- 1, then decrease to 5.5 ± 2.8 µg.ml- 1 and 1.2 ± 0.7 µg.g- 1. We note a great interpersonnal variability of results and particularly for the rectal route. The rectal route seems less effective than the IV route, indeed 25 % of patients show tissue rate greater or equal to MIC90 against 89 % for the IV route.