Pharmacokinetics – Effectiveness is not everything

Pharmacokinetics describes how concentrations of both active substances and their catabolic products in bodily fluids and tissue develop over time. It seeks to understand the biological mechanisms that are responsible for this and uses mathematical models to describe how these mechanisms interact. A drug’s pharmacokinetic properties are crucial to its effectiveness, and during the past few years pharmacokinetic predictions have become an increasingly important aspect of drug development. These predictions can be based on the chemical structure of the substance, measurable chemical properties or on in-vitro data. It is not uncommon for pharmacokinetics to be the last major hurdle that has to be taken before the production of a new blockbuster. Pharmaceutical researchers at Bayer, for example, believe that between 20 and 30 percent of the candidate substances they select do not make it to production owing to the fact that they catabolize too fast inside the body.

As mathematical models have an important role to play in pharmacokinetics, it was only a matter of time before these processes would be simulated too. For ADME (absorption, distribution, metabolism and excretion)-calculations in particular, scientists now want to make greater use of process simulation. The reason is obvious: any measurement that can be simulated on a computer is bound to save time and hence cost far less than if it had to be performed on a living organism, whether on a human or a laboratory animal. Two employees of Bayer Technology Services (BTS), Dr.Walter Schmitt and Dr. Stefan Willmann, have succeeded in developing a software program that will enable pharmaceutical researchers to do just this.
PK-SIM (PK stands for Pharmakokinetics) can describe some 15 different organs such as the liver, heart and brain, in terms of their blood-flow rates, volume, share of fat and protein and arterial surface structure. Nor are these simulations limited to humans; the clinical trials can focus instead on organisms such as mice, rats and dogs. The developers at Bayer are sure that simulated trials will bring about significant reductions in development times and hence a no less significant reduction in costs as well. BTS-Developer Schmitt is surprised that other pharmaceutical companies are not making more of an effort in the field of simulation for pharmakokinetics. “No aircraft, no car and no electronic circuit could be developed today without state-of-the-art simulation,” says Schmitt. The BTS team have turned this fact to their advantage by furnishing PK-SIM with a user-friendly user interface to facilitate external marketing. Perhaps this marks yet another major milestone in the history of drug research and development.

-Mark Platthaus-