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Distribution of antidepressants between plasma and red blood cells

Z Fisar, K Fuksova, J Sikora, L Kalisova, M Velenovska, M Novotna

. 2006 ; 27 (3) : 307-313.

Jazyk angličtina Země Švédsko

Perzistentní odkaz   https://www.medvik.cz/link/bmc13032604

Grantová podpora
NR8408 MZ0 CEP - Centrální evidence projektů

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. MATERIALS AND 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. CONCLUSION: 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.

Bibliografie atd.

Literatura

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$a Fišar, Zdeněk, $d 1956- $7 jn20000400692 $u Department of Psychiatry, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
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$a 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. MATERIALS AND 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. CONCLUSION: 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.
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