Metronidazole kinetics in dialysis patients.

Five volunteers with normal renal function (NOR) and eight patients with renal insufficiency (REN) were given a single dose of 500 mg metronidazole (MET) intravenously over 26 minutes. Serial venous plasma samples were taken at certain intervals for 30 hours. Four of the eight REN patients were also given the drug at the start of hemodialysis and four simultaneous inflow-outflow samples were taken over 4 hours of dialysis. Plasma MET, the acetic acid metabolite (MTAC), and the hydroxymethyl metabolite (MTOH) were determined by high-pressure liquid chromatography assay. Plasma MET over time curves were analyzed with a nonlinear curve-fitting computer program (ASAAM-27) which employed a two-compartment open model. Plasma MET concentrations were similar in the NOR and REN groups. The volumes of distribution for MET--both V1 and Vdss--were similar in the two groups. Moreover, renal insufficiency did not affect the beta half-life (6.5 hours) or the plasma clearance (10.1 L/hr) of MET. Metabolite concentrations peaked at about 12 hours in both groups, but peak MTAC was five times higher in the REN group and peak MTOH twofold higher. Plasma clearance of MET by dialysis averaged 4.0 L/hr at 30 minutes, but thereafter ranged from 2.9 to 4.2 L/hr. Clearance of MTAC ranged from 5.8 to 7.8 L/hr and that of MTOH 2.7 to 5.6 L/hr. We concluded that renal failure does not alter MET disposition but is associated with significant accumulation of the metabolites of MET, possibly requiring a dose reduction. Moreover, an 8-hour hemodialysis eliminates approximately 50% of an administered dose of MET.