Interaction study of the combined use of paroxetine and fosamprenavir-ritonavir in healthy subjects.

Interaction study of the combined use of paroxetine and fosamprenavir-ritonavir in healthy subjects. Research Abstract Details 

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Interaction study of the combined use of paroxetine and fosamprenavir-ritonavir in healthy subjects. Abstract Text:

Manon J van der Lee,Audrey A M Blenke,Gerard A Rongen,Corrien P W G M Verwey-van Wissen,Peter P Koopmans,Cristina Pharo,David M Burger,Manon J van der Lee,Audrey A M Blenke,Gerard A Rongen,Corrien P W G M Verwey-van Wissen,Peter P Koopmans,Cristina Pharo,David M Burger,

Human immunodeficiency virus-infected patients have an increased risk for depression. Despite the high potential for drug-drug interactions, limited data on the combined use of antidepressants and antiretrovirals are available. Theoretically, ritonavir-boosted protease inhibitors may inhibit CYP2D6-mediated metabolism of paroxetine. We wanted to determine the effect of fosamprenavir-ritonavir on paroxetine pharmacokinetics and vice versa and to evaluate the safety of the combination. Group A started with 20 mg paroxetine every day for 10 days; after a wash-out period of 16 days, subjects received paroxetine (20 mg every day) plus fosamprenavir-ritonavir (700/100 mg twice a day) from days 28 to 37. Group B received the regimens in reverse order. On days 10 and 37, pharmacokinetic curves were recorded. Twenty-six healthy subjects (18 females, 8 males) were included. Median (range) age and weight were 44.4 (18.2 to 64.3) years and 68.8 (51.0 to 89.4) kg. Three subjects were excluded (two because of adverse events; one for nonadherence). Addition of fosamprenavir-ritonavir to paroxetine resulted in a significant decrease in paroxetine exposure: the geometric mean ratios (90% confidence intervals) of paroxetine plus fosamprenavir-ritonavir to paroxetine alone were 0.45 (0.41 to 0.49) for the area under the concentration-time curve from 0 to 24 h (AUC(0-24)), 0.49 (0.45 to 0.53) for the maximum concentration of the drug in plasma (C(max)), and 0.75 (0.71 to 0.80) for the apparent elimination half-life (t(1/2)). The free fraction of paroxetine showed a median (interquartile range) increase of 30% (18 to 42%) after the addition of fosamprenavir-ritonavir. The AUC(0-12), C(max), C(min), and t(1/2) of amprenavir and ritonavir were similar to those of historical controls. No serious adverse events occurred. Fosamprenavir-ritonavir reduced total paroxetine exposure by 55%. This is partly explained by protein displacement of paroxetine. We think that this interaction is clinically relevant and that titration to a higher dose of paroxetine may be necessary to accomplish the needed antidepressant effect.

Interaction study of the combined use of paroxetine and fosamprenavir-ritonavir in healthy subjects. Publishing Authors By Initials

MJ van der Lee,AA Blenke,GA Rongen,CP Verwey-van Wissen,PP Koopmans,C Pharo,DM Burger,MJ van der Lee,AA Blenke,GA Rongen,CP Verwey-van Wissen,PP Koopmans,C Pharo,DM Burger,

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Interaction study of the combined use of paroxetine and fosamprenavir-ritonavir in healthy subjects. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Antimicrobial agents and chemotherapy

VOLUME: 51

Page Numbers: 4098-104

Journal Abbreviation: Antimicrob. Agents Chemother.

ISSN: 0066-4804

DAY: 10

MONTH: 09

YEAR: 2007

Interaction study of the combined use of paroxetine and fosamprenavir-ritonavir in healthy subjects. Information

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LANGUAGE: eng

NlmUniqueID: 315061

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AFFILIATION: Department of Clinical Pharmacy, Radboud University Medical Centre Nijmegen, Geert Grooteplein 10, 6525 GA Nijmegen, The Netherlands. m.vanderlee@akf.umcn.nl

Country: United States

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MEDLINETA: Antimicrob Agents Chemother

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