Pharmacokinetics of metronidazole in patients with varying degrees of renal failure.

Twenty-nine patients with varying degrees of renal insufficiency were given a single intravenous dose of metronidazole (500 mg). Plasma and urinary concentrations of metronidazole and two major metabolites were determined using a specific high performance liquid chromatographic assay. The pharmacokinetic parameters of metronidazole elimination half-life, area under the metronidazole concentration against time curve, apparent volume of distribution, metronidazole clearance and predicted degree of accumulation of metronidazole on repeated dosing were not statistically significantly affected by renal inadequacy of any degree. The urinary excretion of metronidazole in patients with moderate or severe renal insufficiency was approximately half the value in healthy volunteers. The renal clearance of metronidazole was significantly greater in healthy volunteers compared to renally insufficient patients, but accounted for less than 10% of the total metronidazole clearance in all groups. The elimination half-life and predicted accumulation (on three times daily dosing) of metabolite I [1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole] were significantly increased with decreasing renal function from 9.2 h and 2.3, respectively, in healthy volunteers to 34 h and 6.7, respectively, in patients with total renal failure. The degree of accumulation of this metabolite on repeated dosing is probably of limited clinical significance in all patients except those with severe or total renal failure for reasons detailed in the text. The elimination half-life and predicted accumulation on three times daily dosing of metabolite II, [2-methyl-5-nitroimidazole-1-acetic acid] increased rapidly with decreasing renal function.(ABSTRACT TRUNCATED AT 250 WORDS)