CYP 450 interactions generally result from one of two processes - inhibition and induction. Induction means that a substance stimulates the synthesis of the enzyme and metabolic capacity is increased. A drug with a high affinity for an enzyme will slow the metabolism of any low affinity drug. Drugs metabolized by CYP 2D6 are amiodarone, haloperidol, selegiline. CYP 1A2 - erythromycin and fluvoxamine are potent inhibitors of this enzyme.
Some substrates are acetaminophen, amitriptyline and propranolol.
The inhibition of CYP 450 isoenzymes by grapefruit juice lasts about 24 hours and occurs in all forms of the juice - fresh fruit and fresh and frozen juice. There is the potential for dangerous arrhytmias for patients taking cisapride, astemizole and terfanadine. Zafirlukast may significantly increase theophylline serum levels resulting in toxicity. Inter-individual variability is significant in all the interactions. Also, remember that if a patient is on several of the weaker inhibitors of an isoenzyme, the effect may be additive, resulting in a clinically significant interaction even though individually each one may be insignificant.