Research The Bayer Scientific Magazin, Edition 28

Bayer research 28    July 2015

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Detox organ: the liver has a very strong effect on the action of a drug product. It filters foreign chemical compounds – such as 

active pharmaceutical ingredients – out of the bloodstream.

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interactions between cells and tissue 

structures through to processes in the 

complete organ and the human organ-

ism as a whole,” says Küpfer.  This work 

produced various software modules that 

doctors and researchers can use in com-

bination. “For example, the models can 

be used to better understand the effects 

of fatty liver disease, a widespread con-

dition, and to test approaches for new 

drug products,” explains Lippert. “Another 

relevant example is the work on damage 

caused to the liver by toxins. It may help 

us characterize and manage the potential 

risks of drug therapies at an earlier stage 

in future.” 

One of the key questions in drug devel-

opment is what the optimum dose is for 

the individual patient, and thus also how 

quickly the liver breaks down an active 

ingredient. The age of the patient and 

his or her place of origin but also any 

previous illnesses and interactions with 

other drug products can all have a seri-

ous impact on this process. In the con-

text of the VLN, Bayer’s experts therefore 

refined their mathematical model further  

with clinical data from surgery patients 

who provided samples of liver tissue. 

These patients received a cocktail of six 

different drugs that are all metabolized 

in different ways. The researchers then 

tracked their path through the body in 

detail. “This allowed us to directly cor-

relate the variability of the enzymatic 

degradation of these active substances 

to the genetic structure and also the cur-

rent enzymatic make-up of the livers of 

these patients,” explains Lippert. “This in-

creases our ability to estimate the influ-

ence that, for example, different genetic 

backgrounds and dietary habits have on 

the dosages that patients require, for 

instance when extrapolating from a Eu-

ropean to a North African or Japanese 

patient.” He and his colleagues were able 

to not only revise and improve their vir-

tual patient model. “We can now make 

even better predictions about which liv-

er parameters can be reliably determined 

solely from a blood sample, for example,” 

adds Küpfer. 

Safe passage through the liver

Before the active ingredient of a tablet reaches its target site in the body, it passes 

through various organs. The liver often plays a key role in this  process. Its job is to 

filter foreign chemical compounds – including active ingredients of drug products 

– out of the blood and render them inactive. How long this  process takes deter-

mines the effect that a drug has in the human body. 

Küpfer. These models for different groups 

of subjects and patients are ultimately 

used in the planning of clinical trials. “The 

better our models reflect the current state 

of knowledge and the more precise our 

model-based predictions are, the fewer 

patients are needed for clinical trials and 

the safer these trials are in the first place,” 

says Lippert, explaining the benefits of 

simulations with virtual humans.

To further improve their models, Bayer 

Technology Services and Bayer Health-

Care are taking part in the Virtual Liver 

Network, or VLN for short. For five years, 

70 research groups from all over Germa-

ny worked together to construct mathe-

matical models of the complex processes 

that take place in the liver. “We modeled 

all relevant biological processes on dif-

ferent levels – from inside the cells via 

Patient data factors into 

 predictive software

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Bayer research 28    July 2015

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Symbiosis between experimental and virtual chemistry: Dr. Mario Lobell, Dr. Andreas Göller  

and Rolf Schönneis (left to right) are working hand in hand to advance the development of 

computer-supported prediction of important properties of drug candidates.

What benefits will the work of the scientific network have for 

 science and the patients? 

There will certainly not be any immediate benefits; what we’re 

talking about here is a cultural change. The project demonstrates 

that modeling and simulation are feasible approaches for complex, 

dynamic biological issues. And we can apply these tools for ques-

tions that are relevant to the pharmaceutical industry, in particular 

when it comes to improving the decision-making in clinical trials.

What’s more, we now have a better understanding of the mecha-

nisms in the liver. For example, we were able to identify biomarkers 

for progression of fatty liver with our methods. Using these models, 

we can focus and prioritize our attention by establishing more 

“ Models help to set 

 priorities”

Adriano 

Henney

refined, verifiable hypotheses which can then be tested in the 

 laboratory, in either animal models or in clinical trials.

What is your overall verdict on the VLN?

We learned a great deal. In particular the work carried out by 

Bayer Technology Services helps us to understand the translation 

of study findings from the laboratory into clinical practice. We 

are establishing a line-of-sight from subcellular studies through 

to the clinical setting, including patient studies. Particularly im-

pressive in my opinion was the way in which the multidisciplinary 

teams came together to tackle some extremely complex issues 

in biomedical science. I am proud to have been involved in the 

program.

research

 talked to biomedicine scientist Dr. Adriano Henney, Executive 

Director, Virtual Physiological Human Institute for Integrative Biomedical 

Research and former Program Director of the Virtual Liver Network (VLN). 

Nevertheless, “it’s not our objective to 

replace animal testing and patient stud-

ies,” says Lippert. The virtual patients and 

virtual laboratory animals can be used to 

optimize trial conditions, minimizing the 

medical risks and saving test animals 

as well as precious time and money.  

“The development of a new drug product 

typically takes about ten to twelve years 

from the initial idea through to market-

ing authorization. Every opportunity to 

accelerate this process or help us make 

decisions when choosing the right de-

velopment candidates or study designs 

could make a significant difference to 

patients who are affected by life-threat-

ening diseases,” says the pharmacometry 

expert. 

The scientists working in drug devel-

opment also rely on virtual support well 

before the clinical trial planning stages, 

Models shorten the time needed 

to develop new medicines

Computer models

  DOSSIER

Bayer research 28    July 2015

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