Senast ändrad: 22 januari 2019

The group includes scientists in veterinary pharmacology, pharmacokinetics and pharmacodynamics. The primary study focus is to derive new concepts of in vivo pharmacology for a sustainable animal and human welfare and improved doping control.

Integrative pharmacology aims at combining qualitative and quantitative methods in the study of the in vivo action of drugs. Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is typically defined in terms of ligand to target binding affinity also in in vivo experimentation, analogous to in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredic­tions of in vivo efficacious exposure and dose.

We have formulated new expressions of the equilibrium (steady state) relationships between target and ligand, and complex and ligand. These equilibrium relationships are easier to interpret than the more commonly used ligand-, target- and complex concentration-time courses. The new expression of EC50 will be a better parameter guiding effective concentration range, for translational purposes, and assessment of in vivo target occupancy-suppression by ligand. In vivo potency points to what parameters need to be taken into account, and particularly that closed-system (in vitro) parameters should not be first choice when ranking compounds in vivo (open system).

Pharmacokinetic/pharmacodynamic reasoning is a prerequisite in clinical practice of registered veterinary and off-label drugs. This is done by means of optimizing dosing protocols and mitigating risks. Quantitative pharmacology might also be used in doping control in order to discriminate drug residues from screening limits, and for assessment of withdrawal times.

Research is primarily supported by the International Pharma Industry. Collaborations are sought via the Fraunhofer-Chalmers Center, numerous pharmaceutical companies, several pre-clinical and clinical research groups at SLU, Swedish and international universities. In addition, networks are established with the Swedish Medical Product Agency (MPA), and branch organizations, such as the Swedish Trotting Association (STC).