Urine testing for drug compatibility

One of the hoped-for benefits of the human genome project is the ability to use data about our genes to determine what drugs will work best for individuals and what drugs should be avoided. This approach assumes that genetics is the sole factor in how a particular drug works. As with many human traits, genetics is only part of the story. Environment also affects how genes are eventually expressed.

 

Physicians, pharmacologists and drug researchers are well aware of the role of a variety of factors that affect how a drug responds. Drugs can interact with dietary factors that might increase or decrease their potency, and can cause some adverse drug effects. Taking more than one drug can lead to interactions with unwanted effects. Controlling for these kinds of factors is routine.

 

Now researchers at the Imperial College London and Pfizer Research and Development suggest that we need to go a step farther. Our bodies are host to a vast number of other organisms, mostly bacteria that live in the human gut, and the precise mix of species can vary considerably from individual to individual. Bacteria can affect how drugs are metabolized, so should be taken into account. One way to do this would be to identify the secondary chemicals produced.

 

A description of all the genes in the DNA of an organism is called the genome. Similarly, a description of all the metabolic products produced by an organism is called the metabolome. In a human, the metabolome would include the metabolic products from human cells as well as those products from the other organisms living in our body. Identifying the specific products related to the use and breakdown of a drug could lead to a better way to determine how well a drug will work for an individual, as well as the most appropriate dosage.

 

A study just published in the Proceedings of the National Academy of Sciences has shown that analyzing metabolites in urine specimens might be one way to peak at the metabolome. The study used 99 healthy male volunteers aged 18 to 64. Urine specimens were collected before and six hours after a dose of the common painkiller acetaminophen, widely known as paracetamol in the UK. The samples were analyzed using ¹H NMR spectroscopy, which allows for identification of a wide variety of chemicals.

 

Acetaminophen metabolism is well understood, so analysis of the by-products excreted in the urine could potentially offer clues to how individuals process it. Variation among the sample was significant, and some of the differences could be attributed to the action of gut bacteria. Some of the observed differences might account for the toxic side-effects of acetaminophen experienced by some.

 

According to the authors of the study, “with a view to the future practicality of this exciting approach, it is also encouraging that the present result was obtained without the potential advantage of a standard diet and using only ‘‘snapshot’’ predose urine samples. Furthermore, we envisage that rapidly growing recognition of the multiple metabolic interactions between humans and their gut symbionts, and the potential significance of the latter in regard to disease, drug efficacy, and adverse drug reactions, will lead to a revolution in the way that drugs are developed. We also envisage that, in certain cases, gut bacteria will be the principal target of drug action, and that in some other cases, gut bacteria will be manipulated by some prior or accompanying treatment in order to improve drug treatment outcomes.”

 

Source: T. Andrew Clayton, David Baker, John C. Lindon, Jeremy R. Everett, and Jeremy K. Nicholson. 2009.  Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism. Proceedings of the National Academy of Sciences 106 (34): 14728-14733.