Plasma hydroxy-metronidazole/metronidazole ratio can detect early changes in hepatic function in ethanol-induced liver injury

Aliment Pharmacol Ther. 1999 Oct;13(10):1335-41. doi: 10.1046/j.1365-2036.1999.00620.x.

Abstract

Aims: To evaluate the usefulness of plasma hydroxy-metronidazole/metronidazole (OH-MET/MET) ratios as a dynamic liver function test in ethanol abusers with or without liver cirrhosis.

Methods: Metronidazole was administered intravenously for 20 min to healthy volunteers, and to patients with alcohol-induced, non-cirrhotic hepatopathy and liver cirrhosis. Plasma concentrations of metronidazole and hydroxy-metronidazole were measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min after the metronidazole infusion.

Results: Patients with non-cirrhotic alcoholic hepatopathy had significantly elevated aminotransferase levels compared to healthy volunteers and Child A patients. Child-Pugh C patients had significantly prolonged prothrombin times when compared to healthy volunteers and patients with non-cirrhotic hepatopathy. Metronidazole metabolism, as measured by the OH-MET/MET ratio following the intravenous administration of 500 mg of the drug, was significantly impaired in all ethanol-abusing individuals, including patients with non-cirrhotic alcoholic hepatopathy.

Conclusions: Metronidazole metabolism was impaired in ethanol abusers, even in the absence of liver cirrhosis, indicating that ethanol was capable of affecting liver function in the early stages of alcohol-induced liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alcohol Drinking / blood*
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / blood*
  • Chromatography, High Pressure Liquid
  • Humans
  • Liver Cirrhosis, Alcoholic / blood
  • Liver Cirrhosis, Alcoholic / physiopathology*
  • Liver Diseases / blood
  • Liver Diseases / etiology
  • Liver Diseases / physiopathology*
  • Liver Function Tests
  • Male
  • Metronidazole / administration & dosage
  • Metronidazole / analogs & derivatives*
  • Metronidazole / blood*
  • Middle Aged

Substances

  • Anti-Infective Agents
  • Metronidazole
  • 1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole