Advanced pharmacokinetic modelling techniques can cut wastage and unnecessary risk exposure in drug development by pre-empting responses to new compounds in ‘virtual’ early-stage clinical trials, the British Pharmacological Society conference in Brighton heard this week.

Speaking in Brighton, Dr Amin Rostami, director of research and development at Simcyp, described how these approaches can help researchers to select the best candidates for human trials and avoid the costly inconclusive outcomes that arise from poor study design.

Simcyp is a spin-out company from the UK’s University of Sheffield that specialises in population-based pharmacokinetic modelling and simulation. Its platform technology is the Population-based ADME (absorption, metabolism, distribution, elimination) Simulator, which can mimic pharmacokinetics in representative virtual populations, based on the client’s in vitro data.

Dr Rostami cited a number of recent clinical trials that had failed properly to assess the impact of genetic differences in the expression of the metabolic enzyme CYP2C9 on patients’ responses to warfarin, the most widely prescribed anticoagulant in North America. A paper showing how pharmacokinetic/pharmacodynamic simulations can help to skirt this kind of problem was published by Dr Rostami and colleagues from the University of Sheffield’s Academic Unit of Clinical Pharmacology in the British Journal of Clinical Pharmacology last July.

Genetic veriations 'pertinant'
Genetic variations are increasingly pertinent to the drug development process, Dr Rostami noted. The US Food and Drug Administration recently expanded the product labelling for warfarin to include information on how genetic make-up affects patients’ responses to the drug.

“Modelling and simulation are crucial when designing studies which impact on rare genotypes or in identifying individuals at extreme risk from adverse reaction,” Dr Rostami said.