Plasma hydroxy metronidazole/metronidazole ratio in anti-HCV carriers with and without apparent liver disease.
OBJECTIVE
To evaluate plasma hydroxy-metronidazole/metronidazole ratio as a dynamic liver function test in HCV-infected individuals with/without liver disease, in the absence of liver cirrhosis.


METHODS
Metronidazole was administered intravenously in healthy volunteers, asymptomatic anti-HCV-positive blood donors, and in chronic hepatitis C patients. Serology to HCV was determined by a second generation assay and confirmed by gelatin particle agglutination test using recombinant antigens C22-3 and C200. Plasma concentration of metronidazole and hydroxy-metronidazole was measured by high performance liquid chromatography in samples collected 5, 10, 20 and 30 min following the end of metronidazole infusion.


RESULTS
Chronic hepatitis C patients had abnormal liver enzymes, while healthy volunteers and anti-HCV-positive blood donors had normal liver biochemistry tests. Plasma metronidazole concentration was similar in all groups studied. Plasma hydroxy-metronidazole/metronidazole ratio was significantly reduced in HCV-infected subjects, an effect observed 10 min after the end of drug infusion.


CONCLUSIONS
Metronidazole clearance is impaired in anti-HCV-positive blood donors and chronic hepatitis C patients, indicating that HCV is capable of affecting liver function at early stages of the disease. The metronidazole clearance test can detect impaired liver function in HCV-infected individuals even in the absence of liver cirrhosis.
Clinical Pharmacology Unit, São Francisco University Medical School, Bragança Paulista, SP, Brazil.
C M
CM
da Silva
F L
FL
David
M N
MN
Muscará
S S
SS
Sousa
J G
JG
Ferraz
G
G
de Nucci
N C
NC
Polimeno
J
J
Pedrazzoli
D000328:Adult; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000097:blood* / Q000175:diagnosis / Q000276:immunology; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008111:Liver Function Tests; D008297:Male; D008795:Metronidazole / Q000097:blood / Q000378:metabolism; D008875:Middle Aged
D008795:Metronidazole