Many pharmaceutical companies state that they would like to predict the bioavailability in humans early in development of a compound. In order to do so, different in vitro screening studies and in vivo (rat, dog) pharmacokinetics studies are performed but are not always predictive enough. New, reliable methods to determine bioavailability in humans are necessary. Aside from providing reliable predictions, these new methods should save time and be cost-effective.

Integrated services

TNO offers several services to study oral bioavailability, such as the TNO gastro-intestinal model (TIM), cellular transporter assays and the pharmacokinetic modelling software TIMpk. Each of these services provides information about an aspect of the processes that determine the bioavailability of oral formulations. By integrating the data, TNO can answer clients’ research questions more thoroughly.

In the past few years, TNO has taken the first steps to integrate the individual services and has developed the TIMpk software. This approach is meant for use with BCS classes 1 and 2 and will be further improved to include classes 3 and 4. This is a clear case for extra investments to create a new product for the pharmaceutical industry.

Towards beter predictions

By integrating various stand-alone services, TNO can make better predictions concerning oral bioavailability. The combination of the gastrointestinal model TIM and in vitro absorption data in a kinetic model could be used to make reliable predictions of the oral bioavailability for BCS class 3 compounds (high solubility and low permeability, l). This data needs to be combined with parameters that describe the distribution and metabolism in the body. Additionally, in vitro transport data has added value to predict possible drug-drug interactions and certainly needs to be integrated in models describing the oral bioavailability and tissue specific distribution.