Cambridge MedChem Consulting

ADME Properties

Optimization of the ADME (Absorption, Distribution, Metabolism, and Excretion) properties of the drug molecule is often the most difficult and challenging part of the whole drug discovery process. The ADME profile will also have a major impact on the likelihood of success of a drug.

See also the section on Formulation, Solubility

Hints that all is not well with the pharmacokinetic profile of a drug candidate.

A General Strategy for Integrating ADME in Drug Discovery

Keeping an eye of molecular properties throughout the drug discovery process is a critical aspect of the process, the focus at different stages is tabulated below.

See Sections on

I’ve added an analysis of the CYP inhibition in ChEMBL

PKPD simulation

XenologiQ have produced a PKPD simulation tool that is described and available for download here This is a tool to analyse in vitro & in vivo ADME & PK data. Predictions for human PK & dose can be made based on available data & assumptions about efficacious concentration. Guidance is given on how secure such projections are likely to be given the nature and congruence of the data available. The training materials include theoretical background, slides, video presentations & test data for hands-on exercises.

Clinical ADME Studies

The FDA have published guidelines for Clinical Drug Interaction Studies this guidance helps sponsors of investigational new drug applications and applicants of new drug applications evaluate drug-drug interactions (DDIs) during drug development and communicate the results and recommendations from DDI studies. these can be supported by in vitro studies In Vitro Metabolism-and Transporter Mediated Drug-Drug Interaction Studies, this guidance is intended to help drug developers plan and evaluate studies to determine the drug-drug interaction (DDI) potential of an investigational drug product.

Worth Reading

In most drug discovery projects sorting out the ADME/T issues is the most challenging part of the project. Handbook of Essential Pharmacokinetics, Pharmacodynamics and Drug Metabolism for Industrial Scientists provides a useful desktop reference for PK/PD issues and can provide answers to questions like "What is the plasma volume of a Guinea Pig?".

If you want an authorative book on the molecular properties of drug like molecules then Drug-like Properties: Concepts, Structure Design and Methods: From ADME to Toxicity Optimization is the book for you.

Last Updated 27 April 2018