Drug Distribution in Brain and Cerebrospinal Fluids in Relation to IC₅₀ Values in Aging and Alzheimer's Disease, Using the Physiologically Based LeiCNS-PK3.0 Model.

ABSTRACT:

Background

Very little knowledge exists on the impact of Alzheimer's disease on the CNS target site pharmacokinetics (PK).

Aim

To predict the CNS PK of cognitively healthy young and elderly and of Alzheimer's patients using the physiologically based LeiCNS-PK3.0 model.

Methods

LeiCNS-PK3.0 was used to predict the PK profiles in brain extracellular (brain_ECF) and intracellular (brain_ICF) fluids and cerebrospinal fluid of the subarachnoid space (CSF_SAS) of donepezil, galantamine, memantine, rivastigmine, and semagacestat in young, elderly, and Alzheimer's patients. The physiological parameters of LeiCNS-PK3.0 were adapted for aging and Alzheimer's based on an extensive literature search. The CNS PK profiles at plateau for clinical dose r

SUBMITTER: Saleh MAA 

PROVIDER: S-EPMC9246802 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature