title: Influence of dose and route of administration on disposition of metronidazole and its major metabolites.
abstract: The influence of dose and route of administration on the kinetics of metronidazole and its major metabolites has been investigated in 8 healthy volunteers given 0.5 and 2.0 g i.v. and p.o. Metronidazole elimination kinetics from plasma could be described by an open two-compartment model. The systemic oral bioavailability of both doses was approximately 1. The total systemic clearance of the intravenous 2.0 g dose was 9% lower than that of the 0.5 g dose (p less than 0.05). There were no significant dose-related differences in volume or rate of distribution. The elimination half-life was similar after the four treatments with metronidazole. The major elimination pathways, renal excretion and hepatic oxidation and glucuronidation, accounted for more than 2/3 of the total systemic clearance. Clearance both by hepatic oxidative metabolism and renal excretion was significantly lower after 2.0 than after 0.5 g i.v., whereas there was no significant difference after the oral doses. The results indicate that a high therapeutic dose of metronidazole may be eliminated at a reduced rate, but this is probably not of clinical importance. No single saturable elimination pathway was identified.
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D001711:Biotransformation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006900:Hydroxylation; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage* / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D008795:Metronidazole