Pharmacogenetics: Drug or prodrug?

We know that different people respond differently to the same drug. For example, a given drug can cause side effects in one person but not in another. Or it can be very effective for someone but much less effective, or not effective at all, for someone else. A number of factors influence how we react to drugs, both in terms of our therapeutic response and in terms of side effects.

To promote optimal treatment for a patient, pharmacogenetic science has set out to establish a process in which each drug choice is based not only on the symptoms and the physician’s diagnoses and professional experience, but also on unique characteristics in the patient’s DNA. Traditionally, we would use trial and error until we found the right combination.

But pharmacogenetics has the potential to provide every patient with the right medication at the right dose at the right time. It may also help determine whether we should administer a drug or a prodrug.

A drug is a medication that is already pharmacologically active when administered: it is the form that most drugs come in. When the drug is metabolized (i.e., converted into one or more compounds through an enzymatic reaction), it will generally become inactive. Drugs can be metabolized by several tissues and organs, such as the kidneys, lungs and intestines, but the main site of metabolism is the liver, which is rich in enzymes.

A prodrug is a medication that the body converts into a pharmacologically active drug after it is administered. Take, for example, Plavix, which is used to prevent heart attacks (and other cardiovascular events). It is inactive when absorbed, but our metabolism has an enzyme that activates it. However, up to 30% of the population is not able to fully activate the drug, which greatly reduces its effectiveness.