In a prospective study 21 patients with
Crohn's disease not responding to standard treatment (
salazosulfapyridine and/or
corticosteroids) received
metronidazole in a dose of 12 to 20 mg per kg
body weight over 6 and 12 months respectively. The objectives were documentation of side effects and pharmacokinetic behaviour of
metronidazole in relation to the course of the disease. In 3 months intervals and 3 months after the end of treatment activity indices were determined, the side effects of
metronidazole were recorded and the
drug plasma concentration was measured. Compliance of
drug intake was excellent (94%). Best-Index decreased to a minimum after 6 months,
orosomucoid after 3 months. Side effects from
metronidazole (
black tongue, dark urine, paraesthesia,
metallic taste, epigastric
pain, skin reactions,
nausea) were reported by over 80% of the patients at any time of the study. Nearly 50% of patients developed paraesthesia, which was still present 3 months after the end of treatment. A mean dose of 15.4 mg per kg corresponded to a mean plasma concentration of 10.9 micrograms/ml of
metronidazole. Plasma concentrations were not related to treatment success nor to the incidence of side effects. Treatment of
Crohn's disease with
metronidazole for longer than 3 months is not recommended both because of lack of additional therapeutic gain and because of the increasing risk of side effects.