Hepatic in vitro metabolism of peptides – An Interview with Ari Tolonen

The magazine Journal of Pharmaceutical and Biomedical Analysis recently published an article involving several of our Admescope colleagues, called 'Hepatic in vitro metabolism of peptides; Comparison of human liver S9, hepatocytes and Upcyte hepatocytes with cyclosporine A, leuprorelin, desmopressin and cetrorelix as model compounds'. Dr. Ari Tolonen, one of the writers of the article, talks about the project that was the grounds for this publication.

My name is Ari Tolonen and I am originally from small village called Muhos, it is about 40 km from Oulu, to which I moved to start my University studies. My training is in analytical organic chemistry. I got my PhD in 2003 from various studies in the field of LC/MS and NMR techniques. Since then, I have been working full time with ADME research, and in early 2011 I ended up founding Admescope, together with some old colleagues. I am a father of two, enthusiastic about football and heavy music, and I also enjoy books, movies, and good food.

I take care of the CEO duties and am heading studies related to drug metabolism and biotransformations. As we grow, I will be focusing on the latter.

We wanted to investigate what would be the main differences when using different hepatic in vitro models for metabolite profiling studies of peptide-like drugs. It has been a topic with not enough discussion in scientific publications, and while the number of peptide-based, new chemical entities has increased a lot in the industry, it is also of high interest to the pharmaceutical industry. So, we chose four peptides with different characteristics and performed in vitro metabolism studies with several different in vitro systems.

The whole work was part of our internal R&D, planned and performed by our team. Juha Jyrkäs, who performed the experimental work, is preparing his PhD thesis under my supervision, so from that angle there is a connection to the local university as well.

Some of the novel metabolic systems were new for us, and it required new tricks to learn how to use them. In the end, we actually left some data out, as were not fully sure that those were obtained with optimal settings. I am proud of the big steps our team has taken forward in all work related to peptides and different modalities with respect to traditional, small, drug-like compounds.

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