Among neuropsychiatric disorders, depression affects 3-16% of the population, and schizophrenia and epilepsy affect approximately 1% of the population, making them extremely common disorders. However, psychotropic drugs, the cornerstone of treatment, show large individual differences not only in pharmacokinetics (PK) but also in pharmacodynamics (PD), such as therapeutic efficacy and adverse drug reactions, and about 30% of patients show resistance to treatment. Therefore, the development of more effective treatment strategies is desired.
Population PK-PD is encompassed by the concept of pharmacometrics, which considers patients as a population and estimates variable parameter values. In addition, population PK-PD analysis can simultaneously and quantitatively elucidate factors that may affect PD in relation to PK variability. Therefore, in the neuropsychiatric area, the elucidation of PK-PD parameters of various drugs and their influencing factors by population PK-PD analysis is effective for the appropriate use of drugs.
Various population PK-PD analyses have been conducted on antipsychotic drugs in schizophrenic patients. In addition, a PK-PD method has been proposed to predict dopamine D₂ receptor occupancy based on the results of positron emission tomography (PET) and the predicted blood drug concentrations obtained from population PK analysis. On the other hand, for antiepileptic drugs, various PK-PD analyses have been studied, and it is important to design drug administration based on the measurement of blood drug concentration. In the field of antidepressants, population PK analysis of novel antidepressants such as SSRIs and SNRIs has been reported, but the prediction of PK-PD is still insufficient due to the complexity of their effects.
In this presentation, I will introduce PK-PD in the field of neuropsychiatry, including our latest findings.