Fluoxetine disposition in patients suffering from chronic hepatitis C treated with interferon alpha

Background and Objectives: Combination therapy with interferon-alpha and ribavirin is considered the treatment of choice for chronic hepatitis C. However, interferon-alpha may induce severe depression It has been suggested that interferon-alpha is able to modify cytochrome P450 (CYP) 1A2 and 2D6 activity. We therefore decided to study the effects of the interferon-alpha-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-alpha-2b therapy. Results: The only statistically Significant difference we observed was a significant reduction in the terminal elimination half-life of fluoxetine (from 4730 to 33.23 hours; p=0.014) after peginterferon-alpha-2b treatment. Conclusion: These data suggest that interferon-alpha may induce, rather than inhibit, the biotransformation of fluoxetine.