Pharmacometrics in Psychiatric Diseases

Novel CNS drug discovery and development approach: model-based integration to predict neuro-pharmacokinetics and pharmacodynamics

“…Depending on the PK, as well as the type of response (inhibition or stimulation), different PK-PD models can be used. With that, it is possible to learn more about factors that play a role in target activation and signal transduction to the ultimate effect or biomarker of the effect [57][58][59][60][61], interspecies differences in concentrationeffect relationships [62], tolerance and sensitization [63], and intra-and interindividual variability. Moreover, for studies with only PK and PD observations but not TO data, a delay between the PK and PD is often be explained by a biophase (or effect compartment) distribution model.…”

“…Currently, to link (neuro-)PK to the systems response, PK-PD modeling is often applied. These models can include target activation (receptor theory [65][66][67][68]), signal transduction [57][58][59][60][61], interspecies differences [62], tolerance and sensitization [63], and intra-and interindividual variability. Also here, it should be noted that parameter values of PK, PD, and disease processes should not be obtained in isolation, and in different systems, because in such manner interrelationships and systems dependencies of processes cannot be assessed.…”

Translational aspects of blood–brain barrier transport and central nervous system effects of drugs: From discovery to patients

“…The ultimate goal of using CNS drugs is to treat a disease with a target in the CNS. One of the first questions is “What can be considered as the target?” Drugs for diseases like epilepsy, Parkinson's disease, Alzheimer's disease, schizophrenia, depression, and anxiety have mostly been developed for neurotransmitter related targets, multiple sclerosis is mostly associated with immune system‐ and inflammation‐related targets, and brain tumors, like all cancers, are mostly associated with biochemical targets that interfere with growth. However, many CNS diseases have multiple distorted components and associated targets, so speaking about one target for a disease is too simple.…”

“…However, many CNS diseases have multiple distorted components and associated targets, so speaking about one target for a disease is too simple. The focus should be on unraveling the disease fingerprint and describing the multiple targets, and if they are not measurable directly, finding biomarkers of the disease and drug effects …”