Chapter 7: The Characteristics, Validation and Applications of In silico and In vitro Models of Drug Transporters

Development of in silico and in vitro models for drug transporter studies is important to understand the pharmacokinetics, assess drug–drug interactions (DDIs) and toxicities, and to recognise variability in drug response due to the involvement of transporters. A large number of different types of in silico and in vitro models are reported in the literature for transporter studies. These models are used as primary screens for new chemical entities and have the potential of high throughput capacity at the early development stage. In vitro models for a drug transporter should be able to determine kinetic parameters (for e.g. K_m, V_max and IC₅₀) of substrates or inhibitors precisely and accurately whilst being a robust system able to be used on a routine basis. This chapter aims to systematically introduce various in silico and in vitro transporter models, comprehensively analyse major models available for transporter studies, and critically outline the advantages, disadvantages and applications of each. Validation of in vitro assays/models and in vitro parameters generated from these models is also discussed in light of their utility in the prediction of drug pharmacokinetics, DDIs and safety.