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Ziprasidone and the activity of cytochrome P450 2D6 in healthy extensive metabolizers
Author(s) -
Wilner K. D.,
Demattos S. B.,
Anziano R. J.,
Apseloff G.,
Gerber N.
Publication year - 2000
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2000.00152.x
Subject(s) - dextromethorphan , dextrorphan , cyp2d6 , ziprasidone , pharmacology , placebo , pharmacokinetics , medicine , anesthesia , cytochrome p450 , antipsychotic , psychiatry , schizophrenia (object oriented programming) , alternative medicine , pathology , metabolism
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.