Het cytochroom P450 enzymsysteem: wat is de relevantie voor de praktijk? Deel II, interacties

In man a great interindividual variability exists in the oxidative capacity to metabolize drugs. A major factor contributing to this phenomenon is the genetically determined hydroxyla-tion-capacity of the cytochrome P450 enzyme system. The cytochrome P450 system comprises of several isozymes. For several isozymes (CYP2D6, CYP2C) a genetically based hydroxylation capacity has been demonstrated. A frequency distribution of the clearance shows a bimodal distribution with poor and extensive metabolizers. Applying standard dosing schemes of the drugs that are predominantly metabolised by these isozymes, a considerable number of patients will be intoxicated because of poor metabolism. In general, cytochrome P450 capacity is limited and substrate-affinity is high. Henceforth cytochrome P450 isozymes are likely targets for pharmacokinetic interactions.