IMPPC Fundación Institut de Medicina Predictiva i Personalitzada del Càncer

      Metabolic Profiling

 

Metabolic profiling gives information about how an individual's body will react to certain substances and will allow decisions to be taken about which type of treatment is appropriate and what dosages should be used.

More about Metabolic Profiling

 It is already known that way that a specific drug interacts with different individuals varies greatly depending on the genetic constitution. An individual's genome dictates how rapidly they eliminate certain environmental substances from the body (food, toxins etc) and the same applies to medicines. Some individuals respond well to treatment, while others show no response or develop unpleasant side-effects.

One example of a very well studied determiner of metabolic response to drug therapies is the family of cytochrome P450 enzymes (CYP450). This family of enzymes affects how fast drugs are broken down in the liver and they are involved in how the body processes about a quarter of known drugs including antidepressants, anticonvulsants, anticoagulants and pain relievers. Exactly what enzymes individuals will have is determined by their genes.

Tests to identify the genotype of a patient are now being used to predict, for instance, which patients are sensitive to adverse side effects. For some drugs, dosage recommendations have been published taking genotype into account. The use of some anti-psychotic drugs for psychiatric in-patients and dosage recommendations for patients being treated for pain relief with codeine are just two well-established examples.
Read more about cytochrome P450 (CYPF450)

Read more about cytochrome p450

The cytochrome P450 (CYP450) genes are a family of genes that produce enzymes in the liver that break down a variety of substances including many drugs. Which P450 enzymes a person has depends on his or her genes (genotype) and this determines how the body deals with many substances including about a quarter of all prescribed drugs.

The involvement of the CYP450 enzymes affect response to a wide range of very commonly used drugs including some beta-blockers used to treat heart disease and high blood pressure, some antidepressants, anticonvulsants and anticoagulants. Research has shown that some of the genes in this family (CYP2D6, CYP2C9 and CYP2C19) are particularly important in oxidative metabolism, in other words in how fast these drugs are broken down.

Roche Diagnostics has recently produced a gene-based microarray test that can identify poor, intermediate and ultra-rapid metabolizers. Further clinical trials are planned on hospital-based psychiatry patients. A report from the Department of Health in the UK suggests that this type of genetic testing would be cost effective for identifying psychiatric in-patients who are prone to side effects from certain drugs and thus allowing doctors to tailor their dosages.

Another example is how different versions of a specific CYP450 iso-enzyme affect the metabolism of codeine, a common analgesic. CYP2D6 converts codeine from an inactive form to an active form. Patients with the form of CYP2D6 that produce high quantities of the enzyme break down the inactive form very quickly and may suffer side effects such as breathing problems from having too much of the active drug in their body. Patients with the form that produces little of the enzyme do not suffer any pain relief but might get side effects from having too much of the inactive codeine in their bodies, which can cause nausea.

Genotype for CYP2D6 varies a lot between individuals and research shows that it also varies significantly between different ethnic groups. The genotyping of this enzyme has allowed the prediction of side effects in poor metabolizers and allowed the Medicines and Healthcare products Regulatory Agency in the UK to publish dosage recommendations for the use of codeine in this group of patients.
Information taken from: The Royal Society: "Personalized medicines: hopes and realities". September 2005