Ontogeny of Oral Drug Absorption Processes in Children

A large proportion of prescribed drugs to children are administered orally. Age-related change in factors affecting oral absorption can have consequences for drug dosing. For each process affecting oral drug absorption, a systematic search has been performed using Medline to identify relevant articles (from inception till February 2012) in humans. This review presents the findings … Continued

The Simcyp Population-based ADME Simulator

The Simcyp® population-based absorption, distribution, metabolism and excretion simulator is a platform and database for ‘bottom-up’ mechanistic modelling and simulation of the processes of oral absorption, tissue distribution, metabolism and excretion of drugs and drug candidates in healthy and disease populations. It combines experimental data generated routinely during preclinical drug discovery and development from in … Continued

Physiologically-based Approaches Towards the Prediction of Pharmacokinetics: In Vitro-In Vivo Extrapolation

In adapting to the challenge to make more informed selection of compounds for development, the pharmaceutical industry is increasingly embracing the application of mechanism-based models and prediction tools for prediction of pharmacokinetic parameters. This review first outlines the concepts and application of the major physiologically based prediction tools to extrapolate clearance, tissue distribution, and rate and extent of absorption from minimal in vitro or … Continued

Time-dependent CYP Inhibition

Time-dependent inhibition (TDI) of CYP refers to a change in potency during an in vitro incubation or dosing period in vivo. Potential mechanisms include the formation of inhibitory metabolites and mechanism-based inhibition (MBI). In vitro experiments are configured to assess TDI and MBI is inferred, at least initially. MBI is more profound after multiple-dosing and the recovery period is independent of … Continued

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