title: Ziprasidone and the activity of cytochrome P450 2D6 in healthy extensive metabolizers.
abstract: OBJECTIVE
  To determine whether ziprasidone alters the metabolizing activity of the 2D6 isoenzyme of cytochrome P450 (CYP2D6).
  
  
  METHODS
  Twenty-four healthy young subjects aged 18-45 years were screened for CYP2D6 metabolizing activity and shown to be extensive metabolizers of dextromethorphan. These subjects were then randomized to receive a single dose of ziprasidone 80 mg, paroxetine 20 mg or placebo, 2 h before receiving a dose of dextromethorphan. Urine samples for the determination of dextromethorphan concentrations were collected over the 8 h period following dextromethorphan dosing, and used for the determination of dextromethorphan/dextrorphan ratios. Blood samples were collected immediately before and up to 10 h after the administration of ziprasidone or paroxetine, and used to derive pharmacokinetic parameters of ziprasidone and paroxetine.
  
  
  RESULTS
  There were no statistically significant changes in the urinary dextromethorphan/dextrorphan ratio in the ziprasidone group or the placebo group. By contrast, there was a 10-fold increase in the urinary dextromethorphan/dextrorphan ratio in the paroxetine group and this differed significantly from those in the ziprasidone and placebo groups (P = 0.0001).
  
  
  CONCLUSIONS
  The findings of this study suggest that ziprasidone does not inhibit the clearance of drugs metabolized by CYP2D6.
authors.affiliation: Department of Clinical Research, Pfizer Central Research, Groton, CT 06340, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Wilner
authors.forename: S B
authors.initials: SB
authors.lastname: Demattos
authors.forename: R J
authors.initials: RJ
authors.lastname: Anziano
authors.forename: G
authors.initials: G
authors.lastname: Apseloff
authors.forename: N
authors.initials: N
authors.lastname: Gerber
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D003915:Dextromethorphan / Q000493:pharmacokinetics; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000097:blood / Q000494:pharmacology; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology; D013844:Thiazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D003915:Dextromethorphan; D004791:Enzyme Inhibitors; D017374:Paroxetine; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D013844:Thiazoles; C092292:ziprasidone