Fluoxetine disposition in patients with chronic hepatitis C treated with interferon-α.

Abstract

BACKGROUND AND OBJECTIVES:

Combination therapy with interferon-α and ribavirin is considered the treatment of choice for chronic hepatitis C. However, interferon-α may induce severe depression. It has been suggested that interferon-α is able to modify cytochrome P450 (CYP) 1A2 and 2D6 activity. We therefore decided to study the effects of the interferon-α-2b pegylated derivative on fluoxetine disposition in patients receiving combination chemotherapy for chronic hepatitis C.

METHODS:

After approval by the institutional ethics committee, 20 adult patients with chronic hepatitis C, but with no history of other liver diseases, were prospectively admitted to the study, which included phenotyping by means of a dextromethorphan test and evaluation of fluoxetine and norfluoxetine pharmacokinetic parameters (the area under the serum concentration-time curve, maximum serum concentration, time to reach the maximum serum concentration and terminal elimination half-life) before and after 2 months of continuous peginterferon-α-2b therapy.

RESULTS:

The only statistically significant difference we observed was a significant reduction in the terminal elimination half-life of fluoxetine (from 47.30 to 33.23 hours; p = 0.014) after peginterferon-α-2b treatment.

CONCLUSION:

These data suggest that interferon-α may induce, rather than inhibit, the biotransformation of fluoxetine.

• Authors: Mario Furlanut, Giorgio Soardo, Debora Donnini, Leonardo Sechi, Loretta Franceschi
• Journal: Clinical pharmacokinetics (Clin Pharmacokinet) Vol. 49 Issue 11 Pg. 767-72 (Nov 2010) ISSN: 1179-1926 [Electronic] Switzerland
• PMID: 20923249 (Publication Type: Journal Article)

Chemical References

• Antidepressive Agents, Second-Generation
• Antiviral Agents
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Fluoxetine
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2b

Topics

• Adult
• Antidepressive Agents, Second-Generation (blood, pharmacokinetics, therapeutic use)
• Antiviral Agents (therapeutic use)
• Area Under Curve
• Drug Interactions
• Drug Therapy, Combination
• Female
• Fluoxetine (blood, pharmacokinetics, therapeutic use)
• Half-Life
• Hepacivirus (drug effects, genetics)
• Hepatitis C, Chronic (drug therapy, genetics, metabolism)
• Humans
• Interferon alpha-2
• Interferon-alpha (therapeutic use)
• Male
• Middle Aged
• Phenotype
• Polyethylene Glycols (therapeutic use)
• Recombinant Proteins
• Ribavirin (therapeutic use)
• Young Adult