Plasma hydroxy-metronidazole/metronidazole ratio can detect early changes in hepatic function in ethanol-induced liver injury.
OBJECTIVE
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.
Da Silva
C M
CM
Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Bragança Paulista, SP, Brazil.
David
F L
FL
Muscará
M N
MN
Sousa
S S
SS
Ferraz
J G
JG
De Nucci
G
G
Polimeno
N C
NC
Pedrazzoli
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000097:blood*; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000503:physiopathology*; D008107:Liver Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood*; D008875:Middle Aged
D000890:Anti-Infective Agents; D008795:Metronidazole; C020910:1-(2-hydroxyethyl)-2-hydroxymethyl-5-nitroimidazole