Urine samples could be used to predict responses to drugs, say researchers

Researchers may be able to predict how people will respond to particular drugs by analysing their urine samples, suggest scientists behind a study published in Proceedings of the National Academy of Sciences.

In the study, researchers from Imperial College London and Pfizer Research and Development showed that it is possible to predict how different individuals would deal with a drug by looking at the levels of different products of metabolism, known as metabolites, in their urine before they took a dose.

This 'metabolic profiling' could ultimately be a valuable tool for predicting how different individuals will react to drugs, enabling drug developers to match drug treatments to individual requirements and avoid adverse side effects. The researchers argue that those developing personalised approaches to medicine will need to consider metabolic as well as genetic profiling when developing drugs.

Metabolic profiles reflect complex gene-environment interactions and the activities of gut bacteria - factors that can influence drug metabolism and toxicity.

Gut microbes live symbiotically in human and animal bodies and there is growing recognition that they play an important part in influencing people's metabolic makeup. The study provides evidence that gut microbes can have a crucial role in determining a person's response to a particular drug.

The researchers looked at 99 healthy male volunteers aged between 18 and 64, taking one dose of the painkiller paracetamol (acetaminophen). They took urine samples from the men before they took the paracetamol and for six hours afterwards and analysed the metabolites in the samples using 1H NMR spectroscopy.

The results revealed that a compound called para-cresol sulphate, derived from para-cresol produced by bacteria in the gut, was an indicator of how the men would metabolise the drug. Those with higher levels of para-cresol sulphate metabolised it in a different way from those with lower levels. The scientists suggest that this is because the body uses compounds containing sulphur to process drugs such as paracetamol effectively and para-cresol can deplete sulphur compounds in the body.

The body uses sulphur to process a variety of drugs, not just paracetamol, so the findings could have significant implications for a whole group of drugs, say the researchers.

They also suggest that where the bacteria in the gut are affecting the body's ability to process a particular drug, it might ultimately be possible to alter the makeup of these bacteria so that the body can process a variety of drugs more effectively and safely.

Professor Jeremy Nicholson, senior author of the study from the Department of Biomolecular Medicine at Imperial College London, said: "Pre-clinical studies had suggested it might be possible to predict how individuals would react to drugs by looking at their pre-dose metabolite profiles, but this is the first time that anyone has been able to show convincingly that such a test could work in humans. The beauty of pre-dose metabolite profiling is that it can tap into both genetic and environmental factors influencing drug treatment outcomes."

Dr Jeremy Everett, vice president of the Research Centres of Emphasis in Pfizer Global Research and Development at Sandwich, UK, and another author of the study, added: "Although this is the first study of its kind and much further research is needed, this finding shows that in the future, researchers may need to consider human metabolic profiles as well as genetic profiles when choosing targets for drug discovery programmes and when selecting patients for future clinical trials."