Safety Pharmacology
Safety pharmacology studies are a key component of novel drug development, and are required to be conducted prior to first time in human clinical trials. Because every compound is unique, it takes specialised knowledge of regulatory guidance and experience to develop the most appropriate safety pharmacology program.
Our experienced safety pharmacologists can provide advice on study selection including addition of safety pharmacology endpoints into other studies, assist with study design, monitor studies, analyse data, contextualise results, review reports and prepare the nonclinical safety pharmacology sections of regulatory submission documents.
The importance of safety pharmacology studies
The aim of safety pharmacology studies is to characterise the pharmacokinetic/pharmacodynamic (PK/PD) relationship of a drug’s adverse effects and to predict the risk of rare lethal events. The cardiovascular, respiratory and central nervous systems are the major organs and systems investigated in core safety pharmacology studies; however, investigations into other organs are also conducted. Early conduct of safety pharmacology screening can help to reduce attrition in later development by aiding selection of the most promising molecules. Bespoke studies can help understanding of the mechanisms of toxicity.
Secondary Pharmacology
In vitro secondary pharmacology screening of small molecules has become standard practice in pharmaceutical research to identify potential off target activity which may give rise to adverse effects. Many drugs are associated with undesirable adverse drug reactions and off target driven toxicity is a significant component of attrition during drug development.
Later profiling of drug candidates may increase understanding of associations between drug molecules adverse drug reactions and biological targets. Our experienced secondary pharmacologists can assist in refining screening strategy, providing data analysis and giving project-specific context to maximise the value of in vitro profiling data for your project.
The association of inhibition of cardiac ion channel, hERG (Kv11.1), with prolongation of the QT interval of the electrocardiogram and linkage to potentially fatal cardiac arrhythmias, while agonist activity at the 5-HT2B receptor has been linked with cardiac valvopathy is well known. In both cases these adverse effects have led to the withdrawal of drugs from the market. Early application of secondary pharmacology screening can help to reduce attrition in later development by aiding selection of the most promising molecules and informing in vivo study design.
Our Secondary Pharmacologist
Dr Duncan Armstrong
PhD
Duncan is an expert pharmacologist with an international reputation in secondary and safety pharmacology, gained over 18 years in drug discovery and development at AstraZeneca and Novartis. Having worked with project teams at all stages of discovery and development across multiple therapy areas, he has a track record of optimising small molecule off-target safety profiles and in understanding and interpreting target-related safety risks. Duncan enjoys bringing his passion for pharmacology to successful collaborative teams.