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Hvidovre Hospital - en del af Københavns Universitetshospital
Udgivet

Influence of dose and route of administration on disposition of metronidazole and its major metabolites

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  • S Loft
  • M Døssing
  • H E Poulsen
  • J Sonne
  • K L Olesen
  • K Simonsen
  • P B Andreasen
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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.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Clinical Pharmacology
Vol/bind30
Udgave nummer4
Sider (fra-til)467-73
Antal sider7
ISSN0031-6970
DOI
StatusUdgivet - 1986

ID: 67020979