For doctors

Pharmacogenetics is a branch of science studying how genes affect pharmacokinetics and pharmacodynamics. Metabolism of pharmaceuticals occurs through enzymes, and genes regulate the expression of enzymes. Currently over 20 genes with clinically significant effects on drug metabolism have been identified. The most important of these are CYP2D6 and CYP2C19 from the CYP enzyme family, and they are associated with significant genetic variation.

Almost everyone has one or more genetic variants that affect their drug metabolism. In a study of over 1000 patients 99 % had at least one genetic variant that affects medication ¹. The prevalence of different genetic variants can vary significantly between populations so that a rare variant in one population can be very common in another. For example, less than half of the Finnish population are considered normal CYP2C19 metabolisers ², which affects the safety and effectiveness of medicines that are metabolised by CYP2C19. Such are, for example, many antidepressants like escitalopram and amitriptyline, as well as the antithrombotic clopidogrel.

The standard dosing guidelines of medicines are based on drug trials where the majority of patients get the desired therapeutic effect. For slower and faster metabolisers, however, the concentration of the medicine can be above or below the therapeutic window. This can lead to not receiving the therapeutic effect (concentration too low) or an increased risk of adverse drug reactions (concentration too high).