14. Detecting pharmacodynamic drug-drug interactions


Team: Dr Tom Jacobs, Prof Luc Bijnens (Janssen), Prof Mauro Gasparini (Politechnico Torino)
Clinical Advisor: Dr Loeckie De Zwart
, an expert in drug metabolism and pharmacokinetics at Janssen and team-leader of the in vivo preclinical PK group.
Location: Janssen Pharmaceutica NV (Beerse, Belgium)

Synergy is a phenomenon describing the potency shift of one or more compounds under combined administration. Synergy between compounds is typically assessed in an in-vitro experiment24 . However, synergy-like behavior can also be observed – deliberately or unexpectedly – in in-vivo experiments especially regarding safety variables25 .

To assess the potential for future co-administration as a new therapeutic option of a new molecule with a marketed product a study co-administering the compounds is undertaken. To estimate the synergy we will use a turnover model26 combined with a latent PK-profile approach27 . This methodology will be applied to a case study, where the co-administration of a novel molecule with an existing, marketed treatment is evaluated. As such, extreme high doses can experimentally used to detect the signs of toxicity due to the drug-drug interaction.

The insights gained from the case study together with extensive simulations will then be used to refine the methodology. Particular attention will be given to the underlying assumptions to robustify the approach. Semi-parametric PK models will be explored as will be ideas around model averaging.

Meet our Early Stage Researcher: Fabiola La Gamba, Janssen Pharmaceutica

Fabiola La Gamba_new

I obtained a BSc in Statistics with a specialization in Biostatistics and an MSc in Biostatistics and Experimental Statistics at the University of Milano-Bicocca, Italy. During my studies I had the opportunity to visit the University of Gent (Belgium) as an exchange student. Also, I undertook an internship in an Italian CRO and a research traineeship at Erasmus University Medical Center of Rotterdam (the Netherlands), where I completed my master thesis. I joined the IDEAS network in June 2015 and I am based in Janssen Pharmaceutica (Belgium), working on nonlinear mixed effects differential equation models in a Bayesian framework and optimal design of experiments. My main hobby is belly dancing, but in general I like all types of ethnic dances and instruments.


24 Tallarida RJ. (2007). Interactions between drugs and occupied receptors. Pharmacol Therapeut, 113(1):197-209.
25 Gasparini M (2013) Journal of the Royal Statistical Society, Series C. 62(1):115-133.
26 Gabrielson J, Weiner D. (2000). Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications. Apotekarsocieteten.
27 Jacqmin P, Snoeck E, van Schaick E, et al. (2007) J Pharmacokinet Phar, 34:57-85.


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