Pharmacokinetic and Pharmacodynamic Effects of Escitalopram Depending on Genetic Polymorphisms of the ABCB1-gene
Status:
Completed
Trial end date:
2018-07-06
Target enrollment:
Participant gender:
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.