Rapid and Robust Pharmacokinetic Prediction for Early Drug Discovery

Absorption, distribution metabolism and elimination (ADME) data play a significant role within the design-make-test-analyse cycle in lead identification and lead optimisation. From the values obtained for individual ADME properties, the DMPK scientist’s goal is to identify compounds that are suitable for progression based on ADME/pharmacokinetic (PK) grounds. The simultaneous assessment of metabolism, permeability and binding data, alongside physicochemical properties such as lipophilicity, polarity and charge can prove difficult. The challenge is to appropriately weigh these multiple data points and combine them into information that can guide decision making on a rational basis. PK prediction is a logical successive step to generation of ADME data, yet few programs or services are currently available that meet the needs of the DMPK scientist in the earliest screening stages.

Cyprotex’s goals are to provide, not only the most accurate in vitro ADME data, but also a means of maximising information content and value to our partners. To address this goal, we have developed a new service for the prediction of human PK from early ADME data. This service provides robust and reliable PK prediction, and meets the requirements of DMPK staff working to tight turn-around schedules. We offer this service, both to partners who utilise our ADME screening services, and those who wish to take advantage of it using their own data.

Briefly, the value of our PK prediction service arises from a combination of:

  1. The range – and hence the utility – of the PK data predicted.
  2. The reliability of the PK predictions, using robust, innovative Cyprotex proprietary methods.
  3. The rapidity of turn-around.
  4. The ease of use of the service’s output.

The service predicts both plasma PK parameters ­and plasma concentrations for intravenous bolus dose or infusion. Thus, whether the objective is to rank and select compounds on PK parameters such as clearance, volume of distribution or half-life, or to use plasma concentrations and/or profiles to drive PK/PD modelling, both are supported and facilitated. Repeat dose regimes, and the approach to steady-state, can be simulated. Test set data show that the predictions for PK parameters and plasma concentrations are reliable whether using metabolic stability data obtained from hepatic microsomes or hepatocytes, enabling compound selection using the results of either in vitro assay.

With short duration make-test-analyse cycles defining the drug discovery timetable, timely use of data is a key determinant of value in the discovery process. Cyprotex’s prediction service meets these requirements for early ADME data, with rapid generation of output that scales from a single compound to hundreds of compounds without additional delay. With output returned in workbooks, containing PK parameters, plasma profile data and plotted plasma profiles, predictions are immediately accessible for review, distribution and presentation.

LEARN MORE about using early ADME data for PK prediction.

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