Clozapine transport into human glioblastoma cells is increased after prolonged incubation with neuroleptic drugs

There is an interindividual variability regarding clinical response to clozapine, depending on age, sex or smoking. Drug metabolism is further effected by the concomitant administration of neuroleptic drugs (1).

To investigate the influence of neuroleptic drugs on clozapine transport, recently demonstrated for promyeloid leukemia cells (2), glioblastoma cells (86HG39) were incubated with 10µM imipramine or haloperidol. Intracellular accumulated clozapine was measured by reversed phase HPLC with electrochemical detection (3).

Incubation of glioblastoma cells with imipramine or haloperidol increased transport of clozapine to about 35% within 14 days. A further increase of transport was not achieved by an extension of incubation time (more than two months). The following incubation in neuroleptic free medium restored transport to its initial capacity.

Assuming that intracellular accumulated drugs have influence on gene expression, comedication might have impact on the cellular effects of clozapine medication in vivo.

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