title: Terbinafine increases the plasma concentration of paroxetine after a single oral administration of paroxetine in healthy subjects.
abstract: OBJECTIVE
  Paroxetine is believed to be a substrate of CYP2D6. However, no information was available indicating drug interaction between paroxetine and inhibitors of CYP2D6. The aim of this study was to examine the effects of terbinafine, a potent inhibitor of CYP2D6, on pharmacokinetics of paroxetine.
  
  
  METHODS
  Two 6-day courses of either a daily 150-mg of terbinafine or a placebo, with at least a 4-week washout period, were conducted. Twelve volunteers took a single oral 20-mg dose of paroxetine on day 6 of both courses. Plasma concentrations of paroxetine were monitored up to 48 h after dosing.
  
  
  RESULTS
  Compared with the placebo, terbinafine treatment significantly increased the peak plasma concentration (C(max)) of paroxetine, by 1.9-fold (6.4 +/- 2.4 versus 12.1 +/- 2.9 ng/ml, p < 0.001), and the area under the plasma concentration-time curve from zero to 48 h [AUC (0-48)] of paroxetine by 2.5-fold (127 +/- 67 vs 318 +/- 102 ng/ml, p < 0.001). Elimination half-life differed significantly (15.3 +/- 2.4 vs 22.7 +/- 8.8 h, p < 0.05), although the magnitude of alteration (1.4-fold) was smaller than C(max )or AUC.
  
  
  CONCLUSIONS
  The present study demonstrated that the metabolism of paroxetine after a single oral dose was inhibited by terbinafine, suggesting that inhibition of CYP2D6 activity may lead to a change in the pharmacokinetics of paroxetine. However, further study is required to confirm this phenomenon at steady state.
authors.affiliation: Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan. yasufuru@cc.hirosaki-u.ac.jp
authors.forename: Norio
authors.initials: N
authors.lastname: Yasui-Furukori
authors.forename: Manabu
authors.initials: M
authors.lastname: Saito
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Inoue
authors.forename: Takenori
authors.initials: T
authors.lastname: Niioka
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.forename: Shoko
authors.initials: S
authors.lastname: Tsuchimine
authors.forename: Sunao
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000284:Administration, Oral; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D017374:Paroxetine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000077291:Terbinafine
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000935:Antifungal Agents; D019389:Cytochrome P-450 CYP2D6; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D009281:Naphthalenes; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000077291:Terbinafine