Why Early ADMET?

Substantial savings of both money and time can be achieved early in the drug discovery process by assaying the ADMET and physico-chemical properties of drug candidates. Early ADMET eliminates wasted developmental effort on unsuitable compounds and directs the focus of medicinal chemistry towards compounds more likely to become successful drug candidates.

High-throughput screening for absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties has become the norm in the drug discovery industry. Just a few years ago, most failures in clinical trials were attributed to ADMET properties rather than efficacy or safety. In recent years, however, the realization of new techniques and refinement of existing techniques have greatly improved the prediction of compounds' pharmacokinetic properties in humans. This has shifted the drug failure attributes more to the safety and efficacy properties of drug candidates.

A tremendous number of tools are available to screen compounds for optimization of ADMET properties and to help discovery scientists select better drug candidates. Apredica’s mission is to assist drug discovery companies with the timing and efficient use of the available ADMET tools to better understand clinical implications and to optimize ADMET properties. Apredica makes your drug discovery efforts as efficient and rational as possible, by doing the right studies at the right time during the hit-to-lead, the early and the late lead-optimization stages of discovery.

What is ADMET?

ADMET is an acronym for Absorption, Distribution, Metabolism, Excretion, and Toxicity. It describes the disposition of a pharmaceutical compound within an organism. These five criteria influence the drug levels and kinetics of drug distribution into the tissues and hence influence the performance and pharmacological activity of the compound as a drug.

Absorption
Absorption determines a compound's bioavailability. Before a compound taken orally can achieve a pharmacological effect it must enter the bloodstream, usually via the digestive tract. From the bloodstream, the compound must achieve uptake into target organs or cells. Some barriers, such as the blood-brain barrier, can substantially prevent this. Factors such as poor compound solubility, chemical instability in the stomach, and inability to permeate the intestinal wall can all limit a drug's absorption properties.

Distribution
The compound needs to be carried to its effector site, most often via the bloodstream. From there, the compound may distribute into tissues and organs, usually to differing extents.

Metabolism
Compounds begin to be metabolized as soon as they enter the body. The majority of small-molecule drug metabolism is carried out in the liver by CYP450 enzymes. As metabolism occurs, the parent drug is converted into metabolites. When metabolites are pharmacologically inert, metabolism deactivates the administered dose of drug, usually reducing its effects. Metabolites may also be pharmacologically active, sometimes more so than the parent drug.

Excretion
Compounds and their metabolites need to be removed from the body via excretion, usually through urine or feces. Unless the compound is completely excreted, its accumulation in the body can adversely affect metabolism.

Toxicity
The potential of a substance to exert a harmful effect on the organism, and a description of the effect, and the conditions or concentrations under which the effect takes place.