Profiles Predict Drug Response

The profile of metabolites present in urine before drugs are administered could help identify whether a patient is a good candidate for a drug, according to a new report.

A team of researchers at Imperial College London, Ume?? University in Sweden, and Pfizer Global R&D report that pre-dose metabolic profiles can predict how an individual might respond to a particular drug (Nature 2006, 440, 1073). Jeremy K. Nicholson and coworkers dub the technique "pharmaco-metabonomics." Unlike pharmacogenomics, pharmaco-metabonomics includes environmental as well as genetic factors.

In this approach, Nicholson and coworkers combine pre-dose metabolite profiles measured by nuclear magnetic resonance spectrometry with mathematical modeling to predict individual responses to drugs. The metabolite profile before a drug is given "carries a lot of latent information about all sorts of potential outcomes, including drug metabolism and toxicity," Nicholson says. "I suspect that we will need several models to cover a range of drug classes."

They measured metabolites in rat urine before and after giving the rats high doses of acetaminophen. They found that individual differences in the metabolism of acetaminophen could be predicted from pre-dose metabolite profiles. Using the levels of several metabolites prior to dosing, they also predicted the kinds of liver damage caused by toxic doses of acetaminophen. "We have shown that there is some connection between the starting metabolic condition of an organism and the outcome of a drug intervention," Nicholson says.

The research "clearly demonstrates the huge potential of proton NMR-based metabonomics," says Ian D. Wilson, a chemist who does metabonomic analyses at AstraZeneca in the U.K. The paper "represents a landmark in the development of the technique and places metabolite profiling firmly up there, with genomics and proteomics, as an essential part of systems biology."