Metabolic Profiling Predicts Drug Responses

Metabolic profiles reflect complex gene-environment interactions and the activities of gut bacteria--factors that can influence drug metabolism and toxicity. In a new study, urine samples from the 99 healthy male volunteers were examined before they took the painkiller acetaminophen, widely known as paracetamol, and for six hours afterwards; the metabolites were analyzed in the samples using 1H NMR spectroscopy.

The results revealed that a compound called para-cresol sulphate, which is derived from para-cresol produced by bacteria in the gut, was an indicator of how the men would metabolize the dose of paracetamol. Those with higher levels of para-cresol sulphate metabolized the drug 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 like 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 new findings about para-cresol could have significant implications for a whole group of drugs. Further work is needed to explore areas such as the relationship between para-cresol and other drugs, and whether para-cresol has any relevance to instances of accidental paracetamol poisoning.

Not all drugs are effective in all patients and occasionally susceptible individuals can have adverse reactions to them. Scientists from Imperial College London (UK) and Pfizer research and development (Sandwich, UK) showed that it was possible to predict how different individuals would deal with paracetamol by measuring levels of metabolites in their urine before taking the drug.

The metabolic profiling could ultimately be a valuable tool for predicting how different individuals will react to drugs, enabling those developing drugs to match drug treatments to individuals' requirements and avoid adverse side effects. New, personalized approaches to medicine will need to consider metabolic as well as genetic profiling when developing drugs, in order to produce a complete picture of different individuals' makeup.

The study was published on August 10, 2009 in the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS).

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Imperial College London
Pfizer