In silico ADME-Tox modeling: progress and prospects

ABSTRACT

Introduction: Although significant progress has been made in high-throughput screening of absorption, distribution, metabolism and excretion, and toxicity (ADME-Tox) properties in drug discovery and development, in silico ADME-Tox prediction continues to play an important role in facilitating the appropriate selection of candidate drugs by pharmaceutical companies prior to expensive clinical trials.

Areas covered: This review provides an overview of the available in silico models that have been used to predict the ADME-Tox properties of compounds. It also provides a comprehensive overview and summarization of the latest modeling methods and algorithms available for the prediction of physicochemical characteristics, ADME properties, and drug toxicity issues.

Expert opinion: The in silico models currently available have greatly contributed to the knowledge of screening approaches in the early stages of drug discovery and the development process. As the definitive goal of in silico molding is to predict the pharmacokinetics and disposition of compounds in vivo by assembling all kinetic processes within one global model, PBPK models can serve this purpose. However, much work remains to be done in this area to generate more data and input parameters to build more reliable and accurate prediction models.

KEYWORDS:

• Absorption
• distribution
• elimination
• in silico modeling
• metabolism
• PBPK modeling
• physicochemical properties

Article highlights

• In silico ADME-Tox prediction continues to play an important role in facilitating the appropriate selection of candidate drugs by pharmaceutical companies prior to expensive clinical trials.

• Early assessment of ADME-Tox properties can minimize the time and cost of screening and testing by identifying the strongest candidates for development and rejecting those with a low probability of success.

• The ultimate goal of in silico modeling of ADME-Tox properties is to predict the in vivo disposition behavior of potential drug molecules in the human body by assembling all kinetic processes into one inclusive model.

• Physiologically Based Pharmacokinetic (PBPK) Modeling integrates all kinetic processes in addition to drug related data to predict and simulate the pharmacokinetics profile of a drug in plasma and tissues.

• Several in silico models have been mentioned in this review; these models could be adapted to help in the advancement of PBPK modeling in the early stages of new chemical entities identification and development.

This box summarizes key points contained in the article.

Declaration of Interest

‘The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.’

Additional information

Funding

The author was supported by the College of Pharmacy Research Center and the Deanship of Scientific Research, King Saud University (Riyadh, Saudi Arabia).