Application of the Nested Enzyme-Within-Enterocyte (NEWE) Turnover Model for Predicting the Time Course of Pharmacodynamic Effects.

ABSTRACT: The gut wall consists of many biological elements, including enterocytes. Rapid turnover, a prominent feature of the enterocytes, has generally been ignored in the development of enterocyte-targeting drugs, although it has a comparable rate to other kinetic rates. Here, we investigated the impact of enterocyte turnover on the pharmacodynamics of enterocyte-targeting drugs by applying a model accounting for turnover of enterocytes and target proteins. Simulations showed that the pharmacodynamics depend on enterocyte lifespan when drug-target affinity is strong and half-life of target protein is long. Interindividual variability of enterocyte lifespan, which can be amplified by disease conditions, has a substantial impact on the variability of response. However, our comprehensive literature

SUBMITTER: Takita H 

PROVIDER: S-EPMC7679071 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature