Founding father of pharmacological models
After 41 years, Meindert Danhof, Professor of Pharmacology, is leaving the Leiden Academic Centre for Drug Research on 31 March. A symposium in his honour, prior to his farewell lecture, will show what has been achieved in this period. Danhof takes a look back on his career.
‘This is an exciting time in Pharmacology,’ says Danhof. After his departure he will continue to be involved in the latest developments in the field: personalised therapies. ‘I want to see that personalised medicines are not something for the happy few, but that the whole population can benefit from them.’ He is organising an international conference in May on the theme of Future Medicines for One World.
‘Go and study pharmacy, then you can become a pharmacist,’ his parents told him when he ended secondary school with high marks for the science subjects – so that’s what he did. But in fact he really wanted to be a pharmacologist, because he was curious about how medicines behave in the body. When Leiden was looking for a pharmacist for PhD research, he took the opportunity to go into research.
At that time, pharmacologists developed mathematical models that describe how medicines are absorbed into the body, distributed and excreted: pharmacokinetics. They were also interested in the question of how medicines work and they made models to describe the relationship between the concentration and effectiveness of medicines. Danhof, who worked for some time in Buffalo (New York, US) after obtaining his PhD, linked the two approaches to create pharmacokinetic-pharmacodynamic models (PKPD models) that show how a medicine works over time.
‘Many pharmacologists were sceptical,’ he explains. But back in Leiden he continued his work at the newly established Centre for Biopharmaceutical Sciences, the precursor of the Leiden Academic Centre for Drug Research. ‘Together with Donald Stanski (Stanford University, California), we managed to determine in free-moving lab animals the course of the concentration and the effect of a medicine. Using these data, we developed a PKPD model that could predict the effect of a new sedative. When I presented this model at an international congress in 1990, it was like a bombshell.’ Today, PKPD models are used routinely in drug development.
As it became clearer how medicines work, pharmacologists started to shift their attention: whereas they had previously aimed to combat symptoms, they now tried to intervene in disease processes. That requires an individual approach for each patient. Danhof: ‘High blood pressure can hide a range of different conditions, each of which requires a different approach. Moreover, people react differently to medicines, and their response changes as they age or as a disease progresses. This calls for precision treatments, and to develop these treatments pharmacologists need to broaden the PKPD models further.’ And that is something he wants to continue to be involved in.