Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Williams RL: Drug administration in hepatic disease. N Engl J Med 309:1616–1622, 1983
Robert RK, Desmond PV, Schenker S: Drug prescribing in hepatobiliary disease. Drugs 17:198–212, 1979
Sherlock S: Chronic hepatitis.In Diseases of the Liver and Biliary System. London, Blackwell Scientific Publications, 1980, pp 270–274
International Group: Acute and chronic hepatitis revisited, Lancet 2:914–919, 1977
Rector WG, Redeker AG: Direct transhepatic assessment of hepatic vein pressure and direction of flow using a thin needle in patients with cirrhosis and Budd-Chiari syndrome. Gastroenterology 86:1395–1399, 1984
Viallet A, Marleau D, Huet PM, Martin F, Farley A, Villeneuve JP, Lavoie P: Hemodynamic evaluation of patients with intrahepatic portal hypertension: Relationship between bleeding varices and the portohepatic gradient. Gastroenterology 69:1297–1300, 1975
Villeneuve JP, Arsène D, Huet PM: Assessment of liver function by the aminopyrine breath test. Clin Invest Med 6:509, 1983
Villeneuve JP, Gerber J, Branch RA, Shand DG, Wilson JT: Drug metabolism in rat bearing a pituitary mammotropic tumor. J Pharmacol Exp Ther 209:7–11, 1979
Branch RA, James JA, Read AE: The clearance of antipyrine and indocyanine green in normal subjects and in patients with chronic liver diseases. Clin Pharmacol Ther 20:81–89, 1976
Huet PM, Villeneuve JP: Determinants of drug disposition in patients with cirrhosis. Hepatology 3:913–918, 1983
Wilkinson GR, Shand DG: A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 18:377–390, 1975
Wilkinson GR, Schenker S: Drug disposition and liver disease. Drug Metabol Rev 4:139–175, 1975
Dudley FJ, Guistino V, Sherlock S: Natural history of hepatitis associated antigen positive chronic liver disease. Lancet 2:1388–1393, 1972
Nation RL, Triggs EJ, Selig M: Lignocaine kinetics in cardiac patients and aged subjects. Br J Clin Pharmacol 4:439–448, 1977
Pirotte J, El Allaf D: Effect of age and sex on theN-demethylation rate of [14C]aminopyrine, studied by the breath test. Digestion 28:210–215, 1985
Wood AJJ, Vestal RE, Wilkinson GR, Branch RA, Shand DG: Effect of aging and cigarette smoking on antipyrine and indocyanine green elimination. Clin Pharmacol Ther 26:16–20, 1979
Geubel AP, Pawels S, Buchet JP, Dumont E, Dive C: Complex liver cell dysfunction in healthy HBsAg carriers. Hepatology 4:1035, 1984 (abstract)
Holoman J, Hadziyannis SJ, Hatzakis A, Ulicna O: Microsomal liver activity in asymptomatic HBsAg carriers. Bratisl Lek Lysty 83:26–34, 1985
Burnstein AV, Galambos JT: [14C]Aminopyrine breath test in chronic liver disease. Preliminary diagnostic implications. Dig Dis Sci 26:1078–1083, 1981
Monroe PS, Baker AL, Schneider JF, Krager PS, Klein PD, Schoeller D: The aminopyrine breath test and serum bile acids reflect histologic severity in chronic hepatitis. Hepatology 2:317–322, 1982
Larrey D, Branch RA: Clearance by the liver: Current concepts in understanding the hepatic disposition of drugs. Semin Liver Dis 3:285–287, 1983
Author information
Authors and Affiliations
Additional information
Supported by grants from the Medical Research Council of Canada, The Canadian Liver Foundation and the Fonds de Recherche en Santé du Québec
Rights and permissions
About this article
Cite this article
Villeneuve, J.P., Thibeault, M.J., Ampelas, M. et al. Drug disposition in patients with HBsAg-positive chronic liver disease. Digest Dis Sci 32, 710–714 (1987). https://doi.org/10.1007/BF01296136
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01296136