Urine test predicts drug response
Metabolic fingerprint could help match medicines to patients.
A simple urine test could show which drugs are best suited to a person's body, say researchers who have shown that the technique works in animals.
The investigators found that the fingerprint of molecules in rat urine foretells whether or not a high dose of the painkiller paracetamol (also called acetaminophen) will poison the animals' livers, because it reveals how well the body can process the drug.
Lead researcher Jeremy Nicholson of Imperial College London says that preliminary tests show a similar analysis works in humans. The team hopes that measuring the molecules in urine could help tailor drug regimens to individuals, avoiding ineffective treatments or dangerous side effects.
Nicholson's team carried out the study in collaboration with researchers at the pharmaceutical company Pfizer, and have published their findings in Nature1.
More than genes
Researchers and drug companies have touted the idea of tailored drug therapies for years, but many have focused on an approach called pharmacogenomics, which matches drugs to a person's genetic make-up.
Nicholson and others argue that this will never work well, because genes say nothing about other factors that affect drug metabolism, such as the types of bugs living in the gut and what we eat for breakfast. "We're finding that genes alone are not enough," agrees Donald Robertson, who studies how metabolism affects drug safety for Pfizer in Ann Arbor, Michigan, but wasn't involved with the study.
Pharmaco-metabonomics, as Nicholson's team call their method, instead takes a snapshot of metabolites, which are produced by the body's network of biochemical reactions.
The team measured the metabolites in the urine of genetically similar rats, before giving the animals a potentially toxic dose of paracetamol. They measured the liver damage in each animal and built a computer model that connected the profiles of metabolites with the damage.
Using a second group of rats, the team tested whether they could predict from urine which animals would suffer liver damage. "Guess what, it works," Nicholson says. "The people at Pfizer fell off their chairs. Nothing from pharmacogenomics has been even close to doing this."
Researchers have talked about this approach for several years, but many assumed it would be difficult to tease out a consistent signature, as metabolites vary from person to person and even from day to day. But Nicholson's experiments suggest that metabolites show significant patterns despite these differences.
Making it better
The researchers don't yet know why certain metabolites appear to predict the body's reaction to drugs. Nicholson says that they probably reflect a person's genetic make-up, the bacteria in their gut and other factors. Diet also affects the body's response to drugs, as might exercise, stress and pollutants.
The technique could potentially be used during clinical trials, to find groups in which a drug ought to work particularly well, or might cause bad side effects.
Nicholson says that a person might even be able to change their metabolic profile to enhance a drug's effects - by, for example, eating probiotic yoghurt that changes the gut bacteria.
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- Clayton T. A., et al. Nature, 440. 1073 - 1077 (2006).
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