Distribution of antidepressants between plasma and red blood cells.
OBJECTIVE
The distribution of different antidepressants between plasma and red blood cells (RBCs) or between water and erythrocyte membranes (ghosts) has not been sufficiently compared so far.


METHODS
Distribution of seven antidepressants (amitriptyline, nortriptyline, imipramine, desipramine, didesmethylimipramine, dothiepin, and citalopram) was measured in vitro in small volumes of blood or erythrocyte membrane suspension using radiolabeled drugs. Blood samples were taken from healthy subjects.


RESULTS
The distribution of antidepressants between plasma and RBCs is strongly affected by temperature; however, it does not depend on the antidepressant concentration in the range of their therapeutic concentrations. The data analysis proved that the ratio of RBCs to plasma volume concentrations is the suitable parameter characterizing antidepressant distribution in whole blood. Significantly higher ratios of RBCs to plasma concentrations were found for demethylated metabolites of tricyclic antidepressants and in the case of citalopram. Citalopram showed the highest accumulation in intact RBCs and at the same time the lowest binding to isolated membranes. The binding of drugs to isolated erythrocyte membranes was much higher than in whole blood.


CONCLUSIONS
The concentration ratio of antidepressant in RBCs and in plasma is sensitive not only to the binding properties of plasma proteins and cell membranes, but also to changes in drug molecule, both in aminopropyl chain and in aromatic rings. This ratio is to a large extent characteristic of a particular antidepressant.
Fisar
Zdenek
Z
Department of Psychiatry, 1st Faculty of Medicine, Charles University, Prague, Czech Republic. zfisar@lf1.cuni.cz
Fuksová
Kvetoslava
K
Sikora
Jan
J
Kalisová
Lucie
L
Velenovská
Marie
M
Novotná
Michaela
M
D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000493:pharmacokinetics*; D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000493:pharmacokinetics*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D010949:Plasma / Q000378:metabolism; D012016:Reference Values; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D014179:Neurotransmitter Uptake Inhibitors