Drug disposition in patients with HBsAg-positive chronic liver disease

Chronic infection with hepatitis B virus (HBV) results in a spectrum of hepatic abnormalities ranging from minimal liver dysfunction to severe liver failure. These patients provide an opportunity to examine the relationship between the evolution of the liver disease and the ability to metabolize dru...

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Bibliographic Details
Published in:Digestive diseases and sciences 1987-07, Vol.32 (7), p.710-714
Main Authors: VILLENEUVE, J. P, THIBEAULT, M. J, AMPELAS, M, FORTUNET-FOUIN, H, LAMARRE, L, COTE, J, POMIER-LAYRARGUES, G, HUET, P.-M
Format: Article
Language:English
Subjects:
Adult
Aminopyrine - metabolism
Antipyrine - metabolism
Biological and medical sciences
Digestive system
Female
Hepatitis - immunology
Hepatitis - metabolism
Hepatitis B Surface Antigens - analysis
Hepatitis, Chronic - immunology
Hepatitis, Chronic - metabolism
Humans
Indocyanine Green - metabolism
Lidocaine - metabolism
Liver - metabolism
Liver Cirrhosis - immunology
Liver Cirrhosis - metabolism
Male
Medical sciences
Metabolic Clearance Rate
Middle Aged
Pharmacology. Drug treatments
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Summary:Chronic infection with hepatitis B virus (HBV) results in a spectrum of hepatic abnormalities ranging from minimal liver dysfunction to severe liver failure. These patients provide an opportunity to examine the relationship between the evolution of the liver disease and the ability to metabolize drugs. We have examined hepatic drug disposition in patients with chronic persistent hepatitis, chronic active hepatitis, and cirrhosis due to HBV infection. Four model drugs were used: two low-extraction capacity-limited drugs (antipyrine and aminopyrine) and two high-extraction flow-limited drugs (ICG and lidocaine). The disposition of the four drugs tested was comparable to that of healthy controls in patients with chronic persistent hepatitis, chronic active hepatitis, and mild cirrhosis. In patients with severe cirrhosis (as defined by the presence of ascites, encephalopathy, or large esophageal varices), there was a significant impairment in the aminopyrine breath test (-31%) and in the clearance of antipyrine (-53%), lidocaine (-49%), and ICG (-54%). These results indicate that impairment of drug clearance occurs only late in the evolution of HBV-related chronic liver disease. This is in keeping with the known slow and insidious progression of the disease.
ISSN:0163-2116
1573-2568
DOI:10.1007/bf01296136