[Genetic polymorphism of the metabolism of drugs used in cardiac diseases].

The genetic determinants of the metabolism of certain drugs used in cardiology is one predictable cause of variability in their pharmacokinetics and effects. Genetic polymorphism of the metabolism of drugs is characterised by the existence of several metabolic phenotypes, usually 2, which allow distinction between fast and slow metabolisers. Clinical identification of these phenotypes is relatively simple. The enzymatic deficiency in slow metabolisers concerns a specific metabolic pathway responsible for the biotransformation of the drug but it respects other eventual metabolic pathways. For a given drug and a given metabolic pathway, slow metabolisers are unable to eliminate the parent product by hepatic metabolism. When the drug is given orally, the plasma concentrations of the parent product in slow metabolisers are 5 to 25 times higher than those observed in fast metabolisers. Depending on the given drug, doses usually well tolerated by fast metabolisers may cause excessive effects in slow metabolisers. The pharmacodynamic consequences of genetic polymorphism on the metabolism of drugs depend essentially on the therapeutic index of the drug concerned and on the activity of the metabolites formed by the genetically determined pathway of the parent product. The pharmacokinetic and pharmacodynamic consequences of the two main genetic polymorphisms concerning drugs used in cardiology are discussed: the polymorphism of N acetylation and that of cytochrome P-450 IID6.