For most antipsychotics, positron emission tomography studies have demonstrated that a therapeutic window of striatal D2 receptor occupancy (65-80%) is associated with clinical response in young adults with schizophrenia. On the other hand, the dopamine D2 receptor occupancy required for the maintenance of remission may be lower than that for acute phase treatment. A series of our modeling work has shown that the dose needed to achieve a target dopamine D2/3 receptor occupancy at peak and trough can be estimated for each individual. First, striatal dopamine D2 receptor occupancy levels with antipsychotics such as risperidone and olanzapine can be predicted from plasma antipsychotic concentrations. Second, doses that result in any given target plasma levels at any point in time can be estimated, using plasma levels of those drugs with two sparsely collected plasma samples with population pharmacokinetic techniques. Furthermore, we demonstrated that by combining these two models, doses that correspond to any given dopamine D2/3 receptor occupancy with risperidone and olanzapine can be reliably estimated for each individual. Thus, in practice, the dose needed to achieve a target D2 receptor blockade at peak and trough can be estimated for each individual and therefore could be used as a target dose.
|ジャーナル||Japanese Journal of Neuropsychopharmacology|
|出版ステータス||Published - 2017 11月 1|
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