Ziprasidone and the activity of cytochrome P450 2D6 in healthy extensive metabolizers

Br J Clin Pharmacol. 2000;49 Suppl 1(Suppl 1):43S-47S. doi: 10.1046/j.1365-2125.2000.00152.x.


Aims: 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / pharmacokinetics*
  • Antipsychotic Agents / pharmacology*
  • Area Under Curve
  • Cytochrome P-450 CYP2D6 / metabolism
  • Cytochrome P-450 CYP2D6 Inhibitors*
  • Dextromethorphan / pharmacokinetics
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Paroxetine / blood
  • Paroxetine / pharmacology
  • Piperazines / blood
  • Piperazines / pharmacokinetics*
  • Piperazines / pharmacology*
  • Selective Serotonin Reuptake Inhibitors / blood
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Thiazoles / blood
  • Thiazoles / pharmacokinetics*
  • Thiazoles / pharmacology*


  • Antipsychotic Agents
  • Cytochrome P-450 CYP2D6 Inhibitors
  • Enzyme Inhibitors
  • Piperazines
  • Serotonin Uptake Inhibitors
  • Thiazoles
  • Paroxetine
  • ziprasidone
  • Dextromethorphan
  • Cytochrome P-450 CYP2D6