TruPK – human pharmacokinetic models for quantitative ADME prediction

Abstract

The use of in silico prediction of absorption, distribution, metabolism and excretion (ADME) properties is gaining acceptance as a useful assessment tool for early identification of likely drug candidate failures. However, it has been difficult to locate reliable models for the prediction of human pharmacokinetics (PK) in silico Currently available methods for estimating ADME and toxicity properties, such as in vitro and animal models, are not very predictive of what is observed in the clinic. Existing in silico ADME prediction tools concentrate on physicochemical properties, such as solubility, log P, rule-of-five compliance, Caco-2 permeability, blood–brain barrier and so on, or only classify drug-like candidates as ‘poor’, ‘medium’ or ‘good’ for a PK parameter, without ascribing values. Although physiology-based pharmacokinetic -models can predict ADME properties, they rely on using various measured properties as input for better accuracy. Strand Genomics has developed a tool, truPK, that predicts the properties of a molecule (bioavailability, protein binding, volume of distribution, elimination half-life and absorption rate) that affect its dose and dose frequency in humans. truPK’s five models built using sophisticated machine methods have predicted with > 75% accuracies in external validation sets.