Enzyme induction, drug-mediated

The metabolic and clinical condition of the patient also plays a role The individual with good kidney and liver function will respond quite differently to a drug than the patient who is not able to detoxify or excrete the compound. The user of laboratory data must be aware of the possible occurrence of drug-mediated enzyme induction, biological variations in the rate of clearance and storage in depot areas (B24), and the genetic factors that play a role in the toxicity of a drug (L2). 

Induction of drug metabolizing enzymes by xenobiotics is an important factor in understanding variations in drug response. Drug-mediated increases in these... 

Fibrates (such as clofibrate) are hypolipidemic drugs. They cause a number of biological and biochemical effects, including enzyme induction, peroxisomal proliferation, liver hypertrophy and hyperplasia, and liver cancer. The mechanism is believed to be mediated through the PPARa receptor. Animals lacking this receptor do not show these effects. 

As the examples cited above indicate, many clinical chug interactions have been considered to be mediated by inhibition or induction of transporters based only on circumstantial evidence. Because of the lack of potent and specific inhibitors for each transporter, it is difficult to accurately assess the relative contributions CYP enzymes and transporters in drug absorption and excretion. The mechanisms become even more complex when multiple CYP enzymes and drug transporters are involved in the processes of drug absorption and excretion. Therefore, care should be taken when exploring the underlying mechanism of drug interactions. 

Drug-drug interactions mediated by enzyme induction are less common than those mediated by enzyme inhibition. Drug-drug interactions due to enzyme induction are also less likely to cause safety issues, except toxic if a toxic metabolite is formed by metabolite activation, however, they may affect... 

St. John s wort is probably effective for mild to moderate but not severe depression. Although well tolerated in most patients, a major concern is its numerous herb-drug interactions mediated by its induction of the cytochrome P450 enzyme system. 

---