Significant dissociation of brain and plasma kinetics with antipsychotics View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-03-01

AUTHORS

J Tauscher, C Jones, G Remington, R B Zipursky, S Kapur

ABSTRACT

Current dosing regimens of psychotropic drugs are based on plasma kinetic considerations, although it is unclear whether plasma levels faithfully reflect brain kinetics of drugs.1,2 To examine this, we compared the kinetics of plasma levels of two widely used antipsychotics, olanzapine and risperidone, vs the time course of their effects in the brain. We used positron emission tomography (PET) and [11C]-labeled ligands to quantify striatal and extra-striatal dopamine-2 (D2), and cortical serotonin-2A (5-HT2A) receptor occupancy in healthy subjects after a single dose, and in patients chronically treated for psychosis. We found a significant dissociation of brain and plasma kinetics. Mean plasma elimination half-lives of single doses of olanzapine and risperidone were 24.2 and 10.3 h, respectively, whereas it took on average 75.2 h with olanzapine, and 66.6 h with risperidone to decline to 50% of their peak striatal D2 receptor occupancy. We found similar discrepancies between the time course of plasma levels and extra-striatal D2 as well as 5-HT2A receptor occupancy. Our results question the current reliance on plasma kinetics as the main basis for dosing regimens of antipsychotics. Studies of brain kinetics may provide a sounder basis for determining dosing schedules of psychotropic medications. More... »

PAGES

317-321

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.mp.4001009

DOI

http://dx.doi.org/10.1038/sj.mp.4001009

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1008693722

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11920159


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