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PII‐63
Author(s) -
Preskorn S. H.,
Baker B.,
KlickDavis A.,
Ramadan M.,
Coyner L.,
Flockhart D. A.,
Desta Z.,
Yang R.,
Burt T.,
Greenblatt D. J.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.188
Subject(s) - escitalopram , sertraline , metoprolol , duloxetine , pharmacokinetics , pharmacology , cyp2d6 , cmax , fluoxetine , drug interaction , citalopram , reuptake inhibitor , duloxetine hydrochloride , chemistry , medicine , cytochrome p450 , antidepressant , receptor , metabolism , serotonin , alternative medicine , pathology , hippocampus
Prior to this study there had been no studies directly comparing the relative effects of duloxetine, escitalopram or sertraline on the functional activity of cytochrome P450 enzyme, 2D6. In this study metoprolol was used as the model substrate drug for CYP2D6. Single‐dose pharmacokinetics of metoprolol were measured before and after 17 days of treatment with escitalopram 20 mg/day, duloxetine 60 mg/day or sertraline 100 mg/day in young healthy male and female volunteers (n=54). The outcome measures were changes in metoprolol peak plasma levels (C max ), area under the plasma concentration‐time curve (AUC) and clearance. The results were tested using paired t‐tests and independent t‐tests. The addition of each drug produced statistically significantly changes in metoprolol pharmacokinetics. The rank order for the change in metoprolol AUC was duloxetine (180%) > escitalopram (89%) > sertraline (48% and 67%). Duloxetine, compared to sertraline, produced statistically significantly larger changes in metoprolol pharmacokinetic parameters. The differences between the changes produced by escitalopram and sertraline were not significant. In summary, each drug produced mild to moderate inhibition of CYP2D6 as reflected in a change in the pharmacokinetics of metoprolol. Clinical Pharmacology & Therapeutics (2005) 79 , P52–P52; doi: 10.1016/j.clpt.2005.12.188