How do drugs transform in the human body and in nature?

What are your research topics?

I study metabolism, or biotransformation, of drug molecules in both humans and environmental organisms. Most drugs are lipophilic, so that they can be absorbed into the body, but through metabolism they are converted into more water-soluble metabolites that are excreted in the urine. Many drugs are metabolized by the same enzymes and may therefore interfere with each other's clearance.

In my research group, we develop cell- and organelle-based in vitro methods to investigate drug-drug as well as drug-enzyme interactions. We utilize microfluidic-based research devices, i.e., microchips, which allow us to create drug concentration profiles similar to those in the human body and to determine whether drug-enzyme interactions are permanent or rapidly reversible. This information is of great importance in clinical use for the safe use of drugs, as long-lasting interactions often complicate the administration of drugs.

Where and how does the topic of your research have an impact?

In drug development, it is particularly important to determine how quickly a drug is metabolized and what kind of metabolites are produced in the body. Although metabolites are mainly water-soluble and inactive, some molecular structures can also form toxic or reactive metabolites. Such metabolites can cause significant side and adverse effects in the user, and naturally we do not want to introduce them into clinical use. The clearance rate is also critical: too fast metabolism prevents the drug from reaching a therapeutic concentration, while too slow metabolism can lead to toxicity.

Individual genetic makeup, lifestyle, age and drug interactions all influence individual metabolic rate. Predicting individual metabolic clearance rates is currently one of the biggest unsolved challenges in the field of personalized medicine. We are therefore developing microfluidic-based diagnostic devices to measure individual differences, utilizing extracellular vesicles isolated from plasma and the biomarkers they carry.

What is particularly inspiring in your field right now?

Drug residues ending up in the environment via human excretions to sewage have become an important research topic. Wastewater treatment plants are unable to effectively remove the diverse drug residues present in very low concentrations. For this reason, drug residues are widely detected in the aquatic environment around the world – most often in densely populated areas.

Although drug metabolism in humans is known and studied very carefully already during the drug development phase, the metabolism of drugs in the environment is currently not well known or even studied, although it is of key importance in terms of the persistence of and the environmental hazards caused by drug residues.

After ending up in the environment, drugs continue to be metabolized at least in two ways. Environmental microbes break down drugs into smaller molecular fragments, and the rate of this microbial metabolism is a key factor in terms of the environmental persistence of the drug. On the other hand, drug metabolism also plays a key role in how drugs accumulate in environmental organisms. For example, fish are continuously exposed to drug residue mixtures in the aquatic environment, and the clearance rate of pharmaceuticals in fish largely determines whether drug residues accumulate in fish tissues. Slow metabolism leads to bioaccumulation, while rapid metabolism reduces the risk. However, there are large differences between species in the rate of metabolic clearance, and drugs can also interfere with each other's metabolism in fish, just as in humans. This makes the assessment of environmental impacts particularly complex. 

In our research group, we investigate these inter-species differences and similarities with the aim of producing information to support future drug development. We hope that our results will help design drugs that are effective and safe for humans but degrade as rapidly as possible in the environment. The ideal future drug candidate could indeed be one that is metabolized at a favorable rate in humans, but particularly rapidly in environmental organisms.