nach oben

Clinical Pharmacokinetics

Erschienen in:

01.11.2010 | Original Research Article

Fluoxetine Disposition in Patients with Chronic Hepatitis C Treated with Interferon-α

verfasst von: Professor Mario Furlanut, Giorgio Soardo, Debora Donnini, Leonardo Sechi, Loretta Franceschi

Erschienen in: Clinical Pharmacokinetics | Ausgabe 11/2010

Einloggen, um Zugang zu erhalten

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.

McHutchinson JG, Gordon SC, Schiff ER, et al. Interferon alfa-2b alone and in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med 1198; 339: 1485–92CrossRef

Manns MP, McHutchinson JG, Gordon SC, et al. Peg-interferon alfa-2b plus ribavirin compared with interferon a-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet 2001; 358: 958–65PubMedCrossRef

Fried MW, Shiffman ML, Reddy RK, et al. Peg-interferon alfa-2b plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347: 975–82PubMedCrossRef

Strader DB, Wright T, Thomas DL, et al., American Association for the Study of Liver Disease. Diagnosis, management and treatment of hepatitis C. Hepatology 2004; 39: 1147–71PubMedCrossRef

Berenguer M. Systematic review of the treatment of established recurrent hepatitis C with pegylated interferon in combination with ribavirin. J Hepatol 2008; 49: 274–87PubMedCrossRef

Reddy KR. Controlled-release, pegylation, liposomal formulations: new mechanisms in the delivery of injectable drugs. Ann Pharmacother 2000; 34: 915–23PubMedCrossRef

Renault PF, Hoof JK, Park Y, et al. Psychiatric complications of long-term interferon alpha-therapy. Arch Intern Med 1987; 147: 1577–80PubMedCrossRef

Kraus MR, Schafer A, Faller H, et al. Psychiatric symptoms in patients with chronic hepatitis C receiving interferon alfa-2b therapy. J Clin Psychiatry 2003; 64: 708–14PubMedCrossRef

Neri S, Pulvirenti D, Bertino G. Psychiatric symptoms induced by antiviral therapy in chronic hepatitis C. Clin Drug Investig 2006; 26: 655–62PubMedCrossRef

10.

Bonaccorso S, Marino V, Puzella A, et al. Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotoninergic system. J Clin Psychopharmacol 2002; 22: 86–90PubMedCrossRef

11.

Abe S, Hori T, Suzuki T, et al. Effect of chronic administration of interferon alpha A/D on serotoninergic receptors in rat brain. Neurochem Res 1999; 24: 359–63PubMedCrossRef

12.

Levenson JL, Fallon HJ. Fluoxetine treatment of depression caused by interferon-alpha. Am J Gastroenterol 1993; 88: 760–1PubMed

13.

Musselman DL, Lawson DH, Gumnick IF, et al. Paroxetine for the prevention of depression induced by high-dose interferon alpha. N Engl J Med 2001; 344: 961–6PubMedCrossRef

14.

Kraus MR, Schafer A, Faller H, et al. Paroxetine for the treatment of interferon-α-induced depression in chronic hepatitis C. Aliment Pharmacol Ther 2002; 16: 1091–9PubMedCrossRef

15.

Raison CL, Woolwine BJ, Demetrashvili MF, et al. Paroxetine for prevention of depressive symptoms induced by interferon-alpha and ribavirin for hepatitis C. Aliment Pharmacol Ther 2007; 25: 1163–74PubMedCrossRef

16.

Islam M, Frye RF, Richards TJ, et al. Differential effect of IFN-a2b on the cytochrome P450 enzyme system: a potential basis of IFN toxicity and its modulation by other drugs. Clin Cancer Res 2002; 8: 2480–7PubMed

17.

Hurst M, Lamb HM. Fluoxetine: a review of its use in anxiety and mixed anxiety and depression. CNS Drugs 2000; 14: 51–80CrossRef

18.

Cheer SM, Goa KL. Fluoxetine: a review of its therapeutic potential in the treatment of depression associated with physical illness. Drugs 2001; 61: 81–110PubMedCrossRef

19.

Spina E, Santoro V, D’Arrigo C. Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update. Clin Therap 2008; 30: 1206–26CrossRef

20.

Hamelin BA, Turgeon J, Vallee F, et al. The disposition of fluoxetine but not sertraline is altered in poor metabolizers of debrisoquin. Clin Pharmacol Ther 1996; 60: 512–21PubMedCrossRef

21.

Ishak K, Baptista A, Bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696–9PubMedCrossRef

22.

Hildebrand M, Seifert W, Reichenberger A. Determination of dextromethorphan metabolizer phenotype in healthy volunteers. Eur J Clin Pharmacol 1989; 36: 315–8PubMedCrossRef

23.

Wong SH, Dellafera SS, Fernandes R. Determination of fluoxetine and norfluoxetine by high-performance liquid chromatography. J Chromatogr 1990; 499: 601–8PubMedCrossRef

24.

Franceschi L, Faggiani A, Furlanut M. A simple method to monitor serum concentrations of fluoxetine and its major metabolite for pharmacokinetic studies. J Pharm Biomed Anal 2009; 49: 554–7PubMedCrossRef

25.

Annesley TM. Ion suppression in mass spectrometry. Clin Chem 2003; 49: 1041–4PubMedCrossRef

26.

Aronoff GR, Bergstrom RF, Pottratz ST, et al. Fluoxetine kinetics and protein binding in normal and impaired renal function. Clin Pharmacol Ther 1984; 36: 138–44PubMedCrossRef

27.

Schenker S, Bergstrom RF, Wolen RL, et al. Fluoxetine disposition and elimination in cirrhosis. Clin Pharmacol Ther 1988; 44: 353–9PubMedCrossRef

28.

Shibata T, Shimada Y, Shymoyama M. Time-dependent cytotoxic action of human recombinant α-interferon (Ro22-8181) in vitro and sensitivity of various cultured leukaemia and lymphoma cell lines to it. Jpn J Clin Oncol 1985; 15: 67–75PubMed

29.

Becquemont L, Chazouilleres O, Serfaty L, et al. Effectofinterferon a-ribavirin biotherapy on cytochrome P450 1A2 and 2D6 and N-acetyltransferase-2 activities in patients with chronic active hepatitis C. Clin Pharmacol Ther 2002; 71: 488–95PubMedCrossRef

Titel: Fluoxetine Disposition in Patients with Chronic Hepatitis C Treated with Interferon-α
verfasst von: Professor Mario Furlanut
Giorgio Soardo
Debora Donnini
Leonardo Sechi
Loretta Franceschi
Publikationsdatum: 01.11.2010
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe 11/2010
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.2165/11534720-000000000-00000

Springer Medizin

Abstract

Background and Objectives

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 11/2010

A Quantitative Framework and Strategies for Management and Evaluation of Metabolic Drug-Drug Interactions in Oncology Drug Development

Pharmacokinetic and Pharmacodynamic Perspectives on the Clinical Drug Development of Panitumumab

Oseltamivir in Seasonal, Avian H5N1 and Pandemic 2009 A/H1N1 Influenza

Plasma Anti-Xa Monitoring for Low-Molecular-Weight Heparins in Patients with Chronic Kidney Disease