title: Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers.
abstract: This study is the first to directly compare the relative effects of duloxetine, escitalopram, and sertraline on the functional activity of the drug-metabolizing cytochrome P450 2D6 enzyme as assessed by changes in the pharmacokinetics of the cytochrome P450 2D6 model substrate drug, metoprolol. Single-dose pharmacokinetics of metoprolol were measured before and after 17 days of treatment with escitalopram 20 mg/d, duloxetine 60 mg/d, or sertraline 100 mg/d in young healthy male and female participants. The outcome measures were changes in metoprolol peak plasma levels, area under the plasma concentration-time curve, and clearance. The results were tested using paired t tests and independent t tests. The addition of each drug produced statistically significant changes in metoprolol pharmacokinetics. The rank order for the change in metoprolol area under the plasma concentration-time curve was duloxetine (180%) > escitalopram (89%) > sertraline (48% and 67%). Compared with sertraline, duloxetine produced statistically significantly larger changes in metoprolol pharmacokinetic parameters. The changes produced by escitalopram and sertraline were not statistically different.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine, KS 67207, USA. spreskorn@cri-research.net
authors.forename: Sheldon H
authors.initials: SH
authors.lastname: Preskorn
authors.forename: David J
authors.initials: DJ
authors.lastname: Greenblatt
authors.forename: David
authors.initials: D
authors.lastname: Flockhart
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.forename: Elke S
authors.initials: ES
authors.lastname: Perloff
authors.forename: Jerold S
authors.initials: JS
authors.lastname: Harmatz
authors.forename: Bryan
authors.initials: B
authors.lastname: Baker
authors.forename: Alisa
authors.initials: A
authors.lastname: Klick-Davis
authors.forename: Zereusenay
authors.initials: Z
authors.lastname: Desta
authors.forename: Tal
authors.initials: T
authors.lastname: Burt
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology*; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects*; D004347:Drug Interactions; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000493:pharmacokinetics; D008875:Middle Aged; D012016:Reference Values; D020280:Sertraline / Q000008:administration & dosage / Q000494:pharmacology*; D016037:Single-Blind Method; D013876:Thiophenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D013876:Thiophenes; D015283:Citalopram; D000068736:Duloxetine Hydrochloride; D019389:Cytochrome P-450 CYP2D6; D008790:Metoprolol; D020280:Sertraline