Modeling of prolactin response following dopamine D₂ receptor antagonists in rats: can it be translated to clinical dosing?

ABSTRACT: Prolactin release is a side effect of antipsychotic therapy with dopamine antagonists, observed in rats as well as humans. We examined whether two semimechanistic models could describe prolactin response in rats and subsequently be translated to predict pituitary dopamine D₂ receptor occupancy and plasma prolactin concentrations in humans following administration of paliperidone or remoxipride. Data on male Wistar rats receiving single or multiple doses of risperidone, paliperidone, or remoxipride was described by two semimechanistic models, the precursor pool model and the agonist-antagonist interaction model. Using interspecies scaling approaches, human D₂ receptor occupancy and plasma prolactin concentrations were predicted for a range of clinical paliperidone and

SUBMITTER: Taneja A 

PROVIDER: S-EPMC5723698 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature