Serum concentrations of metronidazole and its main metabolite in patients with active Crohn's disease: correlation with disease activity and therapeutic efficacy?

Abstract

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.