Wednesday, 16. December 2009

Physiologically-based Modeling of Therapeutic Proteins is now possible with PK-Sim® Version 4.2!

The recently released PK-Sim® version 4.2 enables scientists in pharmaceutical research and development to simulate the pharmacokinetics of therapeutic proteins in one dynamic model integrating both substance specific properties and physiological properties of humans and laboratory animals. This is possible due to a completely new model structure, the two-pore model, developed by computational systems biology experts at Bayer Technology Services.

The technology of physiologically-based pharmacokinetics (PBPK) modeling and simulation has become an essential tool for prudent planning and preparation of studies in animals and humans and supports the crucial go-/no go decision making in research and development of small chemical compounds. With the newly developed two-pore model, it is finally possible to establish this powerful technology in research and development of therapeutic proteins. This enables PK-Sim® users to increase the overall success rates of development projects due to an integrated evaluation of available information on every stage of the development process.

The two-pores model is designed to simulate the pharmacokinetics of macromolecules such as therapeutic proteins. It is an extension of the 4 subcompartments per organ model and contains a description of transcapillary drug exchange according to the two-pore formalism, lymph flows and an additional sub-compartment per organ that represents the endosomal space. The endosomal compartment contains FcRn receptors that are able to protect the macromolecules from catabolism via binding to these receptors (important for e.g. IgG antibodies).

In addition to the two-pore model PK-Sim® 4.2 provides an additional animal model in its database, namely the beagle dog. Animal models play an important role in preclinical development and dogs in particular provide a convenient model for drug and oral dosage-form development since the dimensions of their gastrointestinal tract are similar to humans. Among dogs, beagles are considered the first choice due to their size and friendly nature. For this purpose, a beagle module has been developed and added to the database of animal models in PK-Sim® that now includes models of monkey, mongrel dog, rat, mouse, minipig and the beagle dog.

Another new feature in PK-Sim® 4.2 is an accurate description of peripheral sampling. In clinical practice it is common to sample blood from patients superficial antecubital veins. PK-Sim® 4.2 offers a refined model of the venous blood plasma as a sampling site and is now able to also display the pharmacokinetics of drugs in the peripheral venous plasma. This allows for a more accurate description of clinical data.