An asymptotic description of a basic FcRn-regulated clearance mechanism and its implications for PBPK modelling of large antibodies.

A basic FcRn-regulated clearance mechanism is investigated using the method of matched asymptotic expansions. The broader aim of the work is to obtain further insight on the mechanism, thereby providing theoretical support for future pharmacologically-based pharmacokinetic modelling efforts. The corresponding governing equations are first non-dimensionalised and the order of magnitudes of the model parameters are assessed based on their values reported in the literature.

The PBPK LeiCNS-PK3.0 framework predicts Nirmatrelvir (but not Remdesivir or Molnupiravir) to achieve effective concentrations against SARS-CoV-2 in human brain cells.

SARS-CoV-2 was shown to infect and persist in the human brain cells for up to 230 days, highlighting the need to treat the brain viral load. The CNS disposition of the antiCOVID-19 drugs: Remdesivir, Molnupiravir, and Nirmatrelvir, remains, however, unexplored. Here, we assessed the human brain pharmacokinetic profile (PK) against the EC values of the antiCOVID-19 drugs to predict drugs with favorable brain PK against the delta and the omicron variants.

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

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.