Home |
About Us |
Investor Relations |
Products & Services |
Science & Technology |
People |
News & Events |
Contact Us
Computational Science |
Experimental Science
|
|
 |
|
||
 |
||
| |
|
 |
 |
|
"Virtual physiology" for predicting pharmacokinetics In developing a prediction system for drug pharmacokinetics, we have borrowed from chemical engineers who model the flow of fluids through the pipes and tanks of a chemical production plant so that they can design, test and optimize production units prior to construction. Our comprehensive pharmacokinetic predictor, Cloe® PK can be thought of as a "virtual body" with organs that are modelled as well-stirred tanks connected by pipes - i.e the arteries and veins, which deliver fluid, endogenous materials and drugs. The well-stirred tank model can adequately estimate the flow and distribution of a drug into the organ whilst further refinements divide the organ into a capillary bed through which blood flows. Additional permeability barriers can be included to mimic what happens in the cases of the brain, ovaries and testes which are protected by a tight layer of endothelium. The virtual human also deals with the binding of the drug to plasma protein and its distribution and permeability out of the plasma. Important information that is needed to complete the virtual human includes estimates of the volumes of all organs to be modelled and blood flow to those organs. These values are often scaled by body weight. For absorption modelling, gastro-intestinal transit rates are required, as is information on the radius and internal surface area of the intestine. By changing these parameters virtual rats, dogs and other species can be created. Not only can virtual animal testing improve the chance of success, they also offer an opportunity for drug discovery scientists to reduce their use of live animals. Key organs that modelled include:
Proven accuracy in predicting pharmacokinetics - results from blind trials of Cloe® PK Prediction results closely match those observed in reality - so discovery scientists may confidently make decisions regarding compound design and selection based on Cloe® PK predictions. The impact of pharmacokinetic modelling Today, pharmacokinetic prediction systems can be applied in early drug discovery - to rank compounds according to the most favourable pharmacokinetics and select the best ones for further development, and to perform "virtual screens" of chemical structures in order to create whole libraries that have acceptable pharmacokinetics.  • Comparisons of human in vivo Cloe® PK predictions to clinical data show a close correlation along the 1:1 diagonal line - in this case for human AUC, a key PK parameter. This is an unrivalled level of accuracy which can be of enormous benefit to drug discovery researchers - offering a preferable alternative to testing in animals. Future advancements of the in vivo pharmacokinetic prediction would include the creation of a population of "virtual people" such as would be representative of a group of patients or different racial groups. Virtual populations could be used to warn of the risk of highly variable pharmacokinetics in patients arising from well known genetic variations such as are seen with the liver enzyme CYP2D6. These variations can lead to performance issues for drugs in different populations. In addition, the models will be enhanced to simulate drug-drug interactions and identify potential conflicting therapeutic regimes before the drug has even been given to a patient. It would then be possible to simulate the effect of one drug on another co-administered to a specific individual with normal drug handling properties or to elderly patients, some of which had renal dysfunction, for example. This functionality would greatly benefit the design of clinical trials and marketing of new drugs - since the prediction can identify how the new drug behaves against the competition. |
|
|
 |
|
