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9064
EDTA Blood, 2ml
ABCB1 (ATP-binding cassette sub-family B member 1) is a member of the ATP-binding cassette (ABC) transporter superfamily, which plays a crucial role in the transport of various molecules across cell membranes.
The transporter molecule P-glycoprotein, encoded by the ABCB1 gene, is particularly known for its role in drug transport, as it can pump various drugs out of cells, reducing their effectiveness. This mechanism is often referred to as multidrug resistance (MDR).
Genetic variations in the ABCB1 gene can affect the function and expression of the transporter molecule P-glycoprotein, leading to interindividual differences in drug response.
As the p-glycoprotein is located at the blood-brain-barrier and its substrates include many antidepressant substances like paroxetine, citalopram, venlafaxine and many others (see below), the ABCB1-genotype determines the substrate’s passage ability through the blood-brain-barrier and the subsequent substrate concentration in the brain tissue.
Gene variant 1:
rs2032583 (NM_001348946.2:c.2685+49T>C): CC or CT
rs2235015 (NM_001348946.2:c.287-25G>T): TT or GT
=> Impaired passage of certain antidepressants through the blood-brain barrier
According to studies, suitable antidepressants are therefore either non-substrates of P-glycoprotein or substrates of P-glycoprotein with early application of escalation strategies.
Therapy variant 1: Prescription of one of the following antidepressants (P-gp non-substrates) within the recommended dose range: fluoxetine, mirtazapine, agomelatine, bupropion.
Therapy Variant 2: Prescription of one of the following antidepressants (P-gp substrates) with early use of escalation strategies (e.g. dose increase, augmentation, combination therapy): Paroxetine, citalopram, escitalopram, venlafaxine, amitriptyline, amitriptyline oxide, nortriptyline, trimipramine, sertraline, doxepin, vortioxetine, duloxetine.
Gene variant 2:
rs2032583 (NM_001348946.2:c.2685+49T>C): TT
rs2235015 (NM_001348946.2:c.287-25G>T): GG
=> Facilitated passage of certain antidepressants through the blood-brain barrier
According to studies, suitable antidepressants are substrates of the P-glycoprotein. A prescription should be made within the recommended dose range (ideally accompanied by controls of the plasma level). Since the occurrence of undesirable side effects is increased with the present ABCB1 test result, an overdose of antidepressants should be avoided.
Therapy with substrates of the P-glycoprotein: Paroxetine, citalopram, escitalopram, venlafaxine, amitriptyline, amitriptyline oxide, nortriptyline, trimipramine, sertraline, doxepin, vortioxetine, duloxetine.
Pharmacogenetics
P-glycoprotein
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