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The pharmacokinetics of metronidazole and its metabolites in critically ill patients

K I Plaisance1, R Quintiliani, C H Nightingale

  • 1University of Maryland School of Pharmacy, Baltimore 21201.

The Journal of Antimicrobial Chemotherapy
|February 1, 1988
PubMed

Insights

Critically ill patients with liver and renal dysfunction show altered metronidazole pharmacokinetics. Drug half-life and metabolite elimination are prolonged, impacting treatment effectiveness.

Area of Science:

  • Pharmacology
  • Critical Care Medicine
  • Clinical Pharmacy

Background:

  • Metronidazole is a commonly prescribed antibiotic for anaerobic infections.
  • Its pharmacokinetics can be altered in critically ill patients, particularly those with organ dysfunction.
  • Understanding these changes is crucial for optimizing therapeutic outcomes.

Purpose of the Study:

  • To evaluate the disposition of metronidazole and its metabolites in critically ill patients with hepatic and renal impairment.
  • To determine the impact of liver and kidney dysfunction on metronidazole's half-life and clearance.
  • To assess the elimination patterns of metronidazole's major metabolites under these conditions.

Main Methods:

  • A study involving 14 critically ill patients with liver and renal dysfunction.
  • Administration of 500 mg of intravenous metronidazole for 2-13 days.
  • Pharmacokinetic analysis of metronidazole and its metabolites during and after therapy.

Main Results:

  • Metronidazole half-life varied significantly, ranging from 4.95 to 42.4 hours.
  • Patients with obstructive liver disease had the longest half-lives (9.15-42.4 h) and lowest clearances (0.281-1.17 ml/min/kg).
  • Obstructive liver disease and renal impairment prolonged the elimination of the hydroxymetabolite.

Conclusions:

  • Metronidazole pharmacokinetics are significantly altered in critically ill patients with liver and renal dysfunction.
  • Obstructive liver disease markedly impacts metronidazole's disposition.
  • These pharmacokinetic changes necessitate careful consideration for metronidazole dosing in this patient population.

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