Assessment of the potential for a pharmacokinetic interaction between fluoxetine and terfenadine

Clinical Pharmacology and Therapeutics
R F BergstromB L Hatcher

Abstract

To assess whether fluoxetine and its metabolite, norfluoxetine, are inhibitors of the metabolism of CYP3A substrates. Because inhibition of the first-pass metabolism of terfenadine may be associated with fatal arrhythmia, we assessed the possibility that fluoxetine inhibits this metabolism as a model for CYP3A drug interactions. Male subjects (n = 12) were given two single doses of 60 mg terfenadine alone (treatment 1) and again after the eighth dose in a 9-day regimen of 60 mg fluoxetine once a day (treatment 2). Blood samples, collected up to 48 hours after each terfenadine dose, were assayed for terfenadine and terfenadine acid metabolite. The assay limits of quantification were 0.1 ng/ml and 5.0 ng/ml, respectively. Noncompartmental pharmacokinetic data for terfenadine and terfenadine acid metabolite were compared between treatments. Mean value +/- SD plasma concentrations of fluoxetine (165 +/- 45 ng/ml) and norfluoxetine (83 +/- 23 ng/ml) achieved after the eighth dose did not cause a significant change in terfenadine acid metabolite pharmacokinetics. All terfenadine concentrations were less than 5 ng/ml and they were approximately 30% lower after fluoxetine pretreatment compared with terfenadine alone. The area under the...Continue Reading

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Citations

Jan 4, 2001·Drug Metabolism Reviews·S A WrightonP B Watkins
Nov 28, 2006·Expert Opinion on Drug Metabolism & Toxicology·Emilio SternieriAnna Ferrari
Dec 24, 2011·Expert Opinion on Drug Metabolism & Toxicology·Alexandre ChanKevin Yi-Lwern Yap
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Dec 25, 2009·European Journal of Cancer Care·K Y-L YapA Chan
Jan 6, 2004·Fundamental & Clinical Pharmacology·Edoardo SpinaConcetta D'Arrigo
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Jan 8, 2004·Journal of Clinical Psychopharmacology·C Lindsay DeVaneLauren Willard
Jun 14, 2006·Biopharmaceutics & Drug Disposition·Laurian VlaseMircea Nanulescu
Jul 19, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·C Lindsay DeVane
Aug 5, 2000·Clinical Pharmacokinetics·E L Michalets, C R Williams
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Apr 11, 2001·Therapeutic Drug Monitoring·J LundmarkF Bengtsson
Dec 6, 2016·Current Pharmacology Reports·Barbara Wiśniowska, Sebastian Polak

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