Scientists develop new concept with potential to help predict how individuals may respond to drugs

Research published today in Nature demonstrates the new ‘pharmaco-metabonomic’ approach that uses a combination of advanced chemical analysis and mathematical modelling to predict drug-induced responses in individual patients. The method is based on analysis of the body’s normal metabolic products, metabolites, and metabolite patterns that are characteristic of the individual. The authors hypothesize that these individual patterns can be used to diagnose diseases, predict an individual’s future illnesses, and their responses to treatments.

Not all drugs are effective in all patients and in rare cases adverse drug reactions can occur in susceptible individuals. To address this, researchers from Imperial College and Pfizer have been exploring new methods for profiling individuals prior to drug therapy. The new approach, if successful, requires the analysis of the metabolite profiles of an individual from a urine, or other biofluid, sample.

The researchers tested their approach by administering paracetamol to rats and measuring how it affected their livers and how it was excreted. Before giving the dose they measured the levels of the natural metabolites in the rats’ urine. Metabolites being small molecules produced by normal body functions, they can indicate a body’s drug response. After creating a ‘pre-dose urinary profile’ for each rat, the researchers used computer modelling to relate the nature of the pre-dose metabolite profile to the nature of the post-dose response.

Professor Jeremy Nicholson, from Imperial College London, who led the research, says: “This new technique is potentially of huge importance to the future of healthcare and the pharmaceutical industry. The ‘pharmaco-metabonomic’ approach is able to account for genetic as well as many environmental factors, and other important contributors to individual health such as the gut microfloral activity. These factors strongly influence how an individual absorbs and processes a drug and also influence their individual metabolism, making this new approach the first step towards the development of more personalised healthcare for large numbers of patients.”

The discovery of this new technology for predicting responses to drugs, which is not limited to individual genetic differences, will hopefully be a key component in the pharmaceutical industry’s aim to understand how patients might benefit from more individualised therapies. The new method is expected to be synergistic with existing pharmacogenomic approaches.

The new methodology is in early stage of development and will be studied in humans to evaluate its possible clinical application. The researchers hope this new technique might one day allow doctors to personalise drug treatments for some individuals, providing physicians with the ability to prescribe medicines that will be most effective for certain patient groups, and at a tailored dose-range for maximum efficacy and safety.