Effects of interferon-alpha on cytochrome P-450 isoforms 1A2 and 3A activities in patients with chronic hepatitis C

• Published in: European journal of gastroenterology & hepatology Vol. 10; no. 6; p. 491
• Main Authors: Pageaux, G P, le Bricquir, Y, Berthou, F, Bressot, N, Picot, M C, Blanc, F, Michel, H, Larrey, D
• Format: Journal Article
• Language: English
• Published: England 01-06-1998
• Subjects: Adult; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP1A2 - metabolism; Cytochrome P-450 Enzyme System - metabolism; Drug Interactions; Female; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - metabolism; Humans; Interferon-alpha - pharmacokinetics; Interferon-alpha - therapeutic use; Male; Middle Aged
• ISSN: 0954-691X
• DOI: 10.1097/00042737-199806000-00010

The risk of adverse drug interactions with interferon-alpha has been poorly assessed. The aim of our study was to establish whether administration of interferon-alpha at therapeutic doses in patients with chronic hepatitis C may have significant inhibitory effects on other drug metabolism. The study was focused on cytochromes P-450 1A2 and 3A, two major isoforms involved in the metabolism of numerous substrates.
Eighteen patients with chronic active hepatitis C requiring an interferon-alpha treatment were studied. Cytochrome P-450 1A2 activity was determined on the basis of an in vivo caffeine metabolism study. Cytochrome P-450 3A activity was determined according to in vivo cortisol metabolism into 6-beta-hydroxycortisol. Both activities were determined 1 month before, at initiation and 1 month after interferon-alpha therapy (3 x 10(6) units, three times a week).
There were no significant differences in the caffeine index (CYP 1A2) and in the 6-beta-hydroxycortisol/free cortisol urinary ratio (CYP 3A) before and after alpha interferon treatment
Chronic administration of interferon-alpha at therapeutic doses does not change in vivo cytochrome P-450 1A2 and 3A activities. These results support the suggestion that drugs metabolized by these isoenzymes may be used together with interferon-alpha in patients with chronic hepatitis C without significant risks of drug interactions.