Serum concentrations of
metronidazole and its main metabolite [1-(2-hydroxyethyl)-2-hydroxymethyl-5-
nitroimidazole] have been determined by high performance liquid chromatography in sera of 10 patients with histologically confirmed
ileocolitis Crohn, 7 presenting with highly active disease and pathologically increased
Crohn's disease activity index (CDAI) and 3 with secreting
fistulas but normal CDAI.
Metronidazole serum concentrations showed dose-dependent peak characteristics and ranged between 10.62 +/- 0.95 and 24.88 +/- 3.63 micrograms/ml for a
metronidazole intake of 1,000 mg/day and between 5.04 +/- 1.13 and 9.21 +/- 1.00 micrograms/ml for a daily intake of 400 mg, whereas its metabolite leveled at constant serum concentrations up to 24 h after onset of
therapy, with 7.50 +/- 1.40 micrograms/ml for a
metronidazole intake of 1,000 mg/day and 3.20 +/- 0.60 microgram/ml for an intake of 400 mg/day. Considering the known minimum inhibitory concentration of
metronidazole for anaerobic bacteria involved in
Crohn's disease, this work has shown 400 mg
metronidazole to be the minimum daily dosage. Correlation analysis, although limited by the small number of patients investigated so far, indicated a possible positive correlation between
metronidazole serum concentrations and disease activity (CDAI, r = 0.480) and therapeutic efficacy (delta CDAI, r = 0.430) in
Crohn's disease.