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Fifty-three patients with Crohn's disease were chosen for this study. They were divided into three groups: the first group (19 patients) was treated with metronidazole and had been receiving the drug for at least 1 year; the second group (13 patients) had previously had the same type of long-term treatment but had been off the drug for at least 3 months before entering the study; the third group (21 patients) had never received treatment with metronidazole. The maximum daily dose of metronidazole used was 800 mg. All patients were examined with a broad set of neurophysiologic investigations devised to reveal signs of peripheral neuropathy. No significant difference was found between the three groups. The conclusion was that a daily dose of metronidazole not exceeding 800 mg is well tolerated by patients with Crohn's disease with regard to objective signs of neurotoxicity. A few patients from all three groups showed a raised perception threshold for changes of temperature in the feet (as compared with the department's normal standard). The results of the test were almost identical in the three groups and thus not connected with the metronidazole treatment. During the study, patients were asked about subjective neurologic symptoms such as tingling and numbness. A few patients from all three groups reported such paresthesias from time to time, but they were of a transient nature, not perpetual, and, in patients taking metronidazole, not aggravated despite continuing treatment with unchanged dose.(ABSTRACT TRUNCATED AT 250 WORDS)

We developed methods for measuring metronidazole, its two major metabolites, and tinidazole in serum and urine. After treatment of each sample with an equal volume of 5% perchloric acid, the drugs were separated by reverse-phase highpressure liquid chromatography (retention times, 6 to 18 min). Quantitation was based on spectrometry at 320 nm. These assays were sensitive, rapid, and specific, and recoveries from biological samples were quantitative. Metronidazole and tinidazole were given as rapid intravenous infusions to four healthy human volunteers. The biological half-lives of these two compounds were 5.4 and 11.1 h, respectively. The hydroxy metabolite of metronidazole appeared quickly in serum and was eliminated at a slow rate. The acetic acid metabolite of metronidazole was detected in serum at very low levels and only for a limited time. No metabolic products of tinidazole were found in serum samples. In urine, 43.7% of the administered dose of metronidazole was recovered over a period of 24 h (24.1% of the dose as the hydroxy metabolite, 12.0% as the acetic acid metabolite, and 7.6% as unchanged drug). Only 18.4% of the infused dose of tinidazole was eliminated in urine over a period of 72 h, and no metabolic products were detected.The two nitroimidazoles metronidazole and tinidazole have been used as antiprotozoal agents for many years. These compounds also possess excellent inhibitory activity against anaerobic bacteria (4, 5, 9, 21, 24) and are used increasingly for treatment of infections caused by these microorganisms.Metronidazole is metabolized in the liver mainly by oxidative processes; the two major metabolites excreted in urine are 1-(2-hydroxyethyl) -2 -hydroxy -methyl -5-nitroimidazole(hydroxy metabolite) and 2-methyl-5-nitroimidazole-1-acetic acid (acetic acid metabolite) (20). High-pressure liquid chromatography methods have been developed to measure the parent compound metronidazole and its two major metabolites (6, 12, 25). Measurements of tinidazole by using high-pressure liquid chromatography have also been reported (12,16).We report here a rapid and simple assay involving high-pressure liquid chromatography for quantitation of metronidazole and its two main metabolites in serum and urine; with a slight alteration in the composition of the mobile phase, this assay was also used for quantitation of tinidazole. The