dextromethorphan and ziprasidone

To determine whether ziprasidone alters the metabolizing activity of the 2D6 isoenzyme of cytochrome P450 (CYP2D6).. 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.. 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).. The findings of this study suggest that ziprasidone does not inhibit the clearance of drugs metabolized by CYP2D6.

Topics: Adolescent; Adult; Antipsychotic Agents; Area Under Curve; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Dextromethorphan; Drug Interactions; Enzyme Inhibitors; Female; Humans; Male; Middle Aged; Paroxetine; Piperazines; Selective Serotonin Reuptake Inhibitors; Thiazoles