Important note: Information in this article was accurate in May 2000. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, May 22, 2000
Prepared by AIDS Weekly editors from staff and other reports
"Amprenavir (141W94) is extensively metabolized by P450 cytochromes, specifically, CYP3A4. Because hepatic insufficiency reduces P450 mediated metabolism, the concentrations in plasma of drugs metabolized through this pathway are often increased in subjects with liver disease," said L. Veronese and colleagues at Glaxo Wellcome.
An in-depth probe of this metabolic relationship was conducted by the researchers in a study using 10 each of healthy, severely cirrhotic, and moderately cirrhotic individuals.
Veronese and et al. were able to determine that the area under the plasma concentration curve (AUC) for this study group differed based upon the extent of disease. For patients with severe liver disease, the AUC was more than four times greater than the normal study group. Patients with moderate cirrhosis had a slightly lower AUC value, which was still more than two times greater than normal study group values.
"AUC (0-infinity) was linearly related to the severity of liver disease, as assessed by the Child-Pugh score," Veronese et al. said. Bilirubin was singularly correlated with AUC (0-infinity), they added. Because of this relationship, investigators suggested that bilirubin might be an appropriate marker for predicting amprenavir metabolism in HIV patients with liver diseases.
An additional study finding indicated that alpha (1)-acid glycoprotein levels are lower in patients with liver disease. This glycoprotein is responsible for binding to amprenavir, according to the investigators.
Ultimately, Veronese and colleagues recommended that patients with liver insufficiencies should decrease their amprenavir dosages accordingly based on their Child-Pugh scores.
To read 32 more articles about amprenavir, visit the www.NewsRx.com online database.
The results of this study were published in Antimicrobial Agents and Chemotherapy ("Single-dose pharmacokinetics of amprenavir, a human immunodeficiency virus type 1 protease inhibitor, in subjects with normal or impaired hepatic function," Antimicrob Agents Chemother 2000 Apr;44(4):821-6. The corresponding author is L. Veronese, Laboratory Glaxo Wellcome, Department of Clinical Pharmacology, F-78163 Marly Le Roi, France.
Key points reported in this study are:
This article was prepared by AIDS Weekly editors from staff and other reports.
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