Pharmacokinetic and Pharmacodynamic Effects of Escitalopram Depending on Genetic Polymorphisms of the ABCB1-gene
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| N/A |
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Time spent in rapid-eye-movement (REM) sleep assessed by polysomnography. [after 6 days of intake of escitalopram]
Time spent in rapid-eye-movement (REM) sleep assessed by polysomnography.
Secondary Outcome Measures
- Sleep stages [after 6 days of intake of escitalopram]
Sleep stages beside REM sleep (wake, NonREM sleep) assessed by polysomnography
- Sleep continuity [after 6 days of intake of escitalopram]
Sleep continuity measures assessed by polysomnography
- ABCB1 gene expression [baseline and after 6 days of intake of escitalopram]
messenger ribonucleic acid (mRNA) expression of the target gene ABCB1
- Metabolic changes [baseline and after 6 days of intake of escitalopram]
Small molecule metabolic changes in blood serum
Eligibility Criteria
Criteria
Inclusion Criteria:
- healthy males 20-30 years
Exclusion Criteria:
- any medication
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Max Planck Institute of Psychiatry | Munich | Germany | 81667 |
Sponsors and Collaborators
- Max-Planck-Institute of Psychiatry
Investigators
- Principal Investigator: Axel Steiger, MD, Max-Planck-Institute of Psychiatry
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- L3/2005