Pharmacokinetic and Pharmacodynamic Effects of Escitalopram Depending on Genetic Polymorphisms of the ABCB1-gene

Blood-brain-barrier Permeability of Escitalopram Depending on Genetic Polymorphisms of the ABCB1-gene: Effect on Sleep and Procedural Learning

The ABCB1-gene product P-glycoprotein is an integral membrane protein that actively transports substrates out of the intracellular compartment. One of the major sites of its action is the blood-brain-barrier. It is highly expressed in brain capillary endothelial cells and involved in limiting the access of substrates such as antidepressants to the central nervous system. A single nucleotide polymorphism (SNP) of the ABCB1-gene was recently identified showing a different treatment response to antidepressant drugs depending on the genotype. Therefore, it is assumed that healthy subjects with different genotypes of that SNP will be associated with significantly different brain levels of the antidepressant escitalopram after 6 days of intake. Sleep recordings are a useful bio-marker for effects of antidepressants on the CNS. Selective serotonin reuptake inhibitors (e.g. escitalopram) cause a suppression of REM sleep and a stronger fragmentation of sleep compared to untreated subjects. Higher plasma levels of antidepressants affected the sleep to a greater extent than lower levels. In line with this finding, we suppose that sleep EEG recordings of healthy subjects with different genotypes of the above mentioned SNP will be differently affected after taking 6 days escitalopram. In addition, effects of drug intake on the gene expression in lymphocytes and metabolic changes will be assessed.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: escitalopram

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Munich, Germany, 81667
    • Max Planck Institute of Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 30 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• healthy males 20-30 years

Exclusion Criteria:

• any medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1; Healthy subjects with a single nucleotide polymorphism (SNP) of the ABCB1-gene (Genotype A)	Drug: escitalopram; escitalopram 4 mg
Other: 2; Healthy subjects with a single nucleotide polymorphism (SNP) of the ABCB1-gene (Genotype B)	Drug: escitalopram; escitalopram 4 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time spent in rapid-eye-movement (REM) sleep assessed by polysomnography.	Time spent in rapid-eye-movement (REM) sleep assessed by polysomnography.	after 6 days of intake of escitalopram

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sleep stages	Sleep stages beside REM sleep (wake, NonREM sleep) assessed by polysomnography	after 6 days of intake of escitalopram
Sleep continuity	Sleep continuity measures assessed by polysomnography	after 6 days of intake of escitalopram
ABCB1 gene expression	messenger ribonucleic acid (mRNA) expression of the target gene ABCB1	baseline and after 6 days of intake of escitalopram
Metabolic changes	Small molecule metabolic changes in blood serum	baseline and after 6 days of intake of escitalopram

Collaborators and Investigators

• Sponsor: Max-Planck-Institute of Psychiatry
• Investigators: Principal Investigator: Axel Steiger, MD, Max-Planck-Institute of Psychiatry

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): July 6, 2018
• Study Completion (Actual): July 6, 2018

Study Registration Dates

• First Submitted: October 29, 2007
• First Submitted That Met QC Criteria: October 29, 2007
• First Posted (Estimate): October 30, 2007

Study Record Updates

• Last Update Posted (Actual): March 27, 2019
• Last Update Submitted That Met QC Criteria: March 25, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: L3/2005