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Clinical Trial
. 2016 Sep;55(9):1115-27.
doi: 10.1007/s40262-016-0389-0.

Lack of Effect of Vortioxetine on the Pharmacokinetics and Pharmacodynamics of Ethanol, Diazepam, and Lithium

Grace Chen  1 , George G Nomikos  2 , John Affinito  3 , Zhen Zhao  4
Affiliations
Clinical Trial

Lack of Effect of Vortioxetine on the Pharmacokinetics and Pharmacodynamics of Ethanol, Diazepam, and Lithium

Grace Chen et al. Clin Pharmacokinet. 2016 Sep.

Abstract

Introduction: Because the multimodal antidepressant vortioxetine is likely to be coadministered with other central nervous system (CNS)-active drugs, potential drug-drug interactions warrant examination.

Objective: These studies evaluated whether there are pharmacokinetic and/or pharmacodynamic interactions between vortioxetine and ethanol, diazepam, or lithium.

Methods: This series of phase I studies included healthy men and women (only men in the lithium study) aged 18-45 years. The ethanol study was a randomized, double-blind, two-parallel group, four-period crossover study in which subjects received a single dose of vortioxetine (20 or 40 mg) or placebo with or without ethanol, and the diazepam study was a randomized, double-blind, placebo-controlled, two-sequence, two-period crossover study in which subjects received a single dose of diazepam following multiple doses of vortioxetine 10 mg/day or placebo. These two studies evaluated the effect of coadministration on standardized psychomotor parameters and on selected pharmacokinetic parameters of each drug. The lithium study was a single-blind, single-sequence study evaluating the effect of multiple doses of vortioxetine 10 mg/day on the steady-state pharmacokinetics of lithium.

Results: Concomitant administration of vortioxetine and single doses of either ethanol or diazepam had no significant effect on the psychomotor performance of subjects compared with administration of ethanol or diazepam alone. Vortioxetine had no significant effect on the pharmacokinetics of ethanol, diazepam, or lithium, and ethanol had no significant effect on the pharmacokinetics of vortioxetine.

Conclusions: Concomitant administration of these agents with vortioxetine was generally well tolerated, with no clinically relevant drug-drug pharmacokinetic or pharmacodynamic interactions identified.

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Conflict of interest statement

Compliance with Ethical Standards Funding These studies were supported by the Takeda Pharmaceutical Company Ltd, and H. Lundbeck A/S. Assistance with writing and manuscript preparation was provided by Bret Fulton, RPh, of The Medicine Group, and funded by the Takeda Pharmaceutical Company Ltd and H. Lundbeck A/S. Conflicts of interest Grace Chen, George G. Nomikos, John Affinito, and Zhen Zhao are employees of Takeda Development Center Americas, Inc. Ethical approval These studies were conducted in accordance with the World Medical Association Declaration of Helsinki, the ICH Harmonised Tripartite Guideline for Good Clinical Practice, and all applicable local regulations. Site-designated investigational review boards approved the protocols. Informed consent Written informed consent was obtained from all individual participants included in the studies.

Figures

Fig. 1
Fig. 1
Effects of multiple once-daily doses of vortioxetine 10 mg on the pharmacokinetics of diazepam and lithium, and of a single dose of vortioxetine 40 mg on the pharmacokinetics of ethanol. AUC last area under the plasma concentration–time curve from time zero to time of the last quantifiable concentration, AUC 12 AUC from time zero to 12 h, CI confidence interval, C max maximum plasma concentration, PK pharmacokinetic
Fig. 2
Fig. 2
Mean change from baseline in digit vigilance speed when a single dose of vortioxetine 20 mg (top) or 40 mg (bottom) was coadministered with ethanol. Error bars represent standard error. LS least squares
Fig. 3
Fig. 3
Mean change from baseline in postural stability when a single dose of vortioxetine 20 mg (top) or 40 mg (bottom) was coadministered with ethanol. Error bars represent standard error. LS least squares
See this image and copyright information in PMC

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