Drug Interaction - Enzyme Induction

Perpetrators of Drug-Drug Interactions Enzyme Induction... 

Chapter II.J Drug-Drug Interaction - Enzyme Induction 545... 

Compared to the benzodiazepine sedative-hypnotics, secobarbital is more lethal in overdosage, has a higher tendency for abuse and addiction, and is more likely to cause drug interactions via induction of hepatic microsomal enzymes few advan-fages if any in safety or efficacy over benzodiazepines... 

Interactions. Enzyme induction of CYP 3A, e.g. by rifampicin, reduces the plasma concentration of itraconazole. Additionally, its affinity for several P450 isoforms, notably CYP 3A4, causes it to inhibit the oxidation of a number of drugs, including phenytoin, warfarin, cyclosporine, tacrolimus, midazolam, triazolam, cisapride and terfenidine (see above), increasing their intensity and/or duration of effect. 

The results of an interaction study between bicalutamide and phenazone suggest that bicalutamide is unlikely to interact with other drugs through enzyme induction. 

Only a small number of drug interactions have been reported with donepezil. In vitro studies show a low rate of binding of donepezil to cytochrome P-450 (CYP)3A4 or 2D6. Whether or not donepezil has the potential for enzyme induction is not known. No interactions with theophylline, cimeti-dine, warfarin, digoxin, or ketoconazole have been documented. In vitro studies show that inhibitors of CYP3A4 and 2D6 have the potential to inhibit the metabolism of donepezil. The clinical relevance of this is unknown. However, monitoring for possible increased peripheral side effects is advised... 

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

Keto con azole Inhibits several 200 mg twice reactions develops with continued use. Hematologic disturbances and hypothyroidism also seen. Generally well High potential for drug interactions due to potent induction of hepatic enzymes. Effective in a majority of causes ... 

Drug-drug interactions have always been major concerns to the pharmaceutical industry. Several prominent drugs were withdrawn from the market because of serious adverse events related to drug-drug interactions. These interactions create problems for clinicians and patients and economic losses for pharmaceutical manufacturers. For this reason, pharmaceutical companies screen for enzyme inhibition and induction at the discovery stage. 

Determine the drug interaction potential when concurrent medications are administered, as well as food interaction, assess the enzyme induction potential, and assess the need for therapeutic drug monitoring during efficacy testing. 

CYP enzymes are induced, resulting in reduced plasma drug levels. Alternatively, CYP enzymes could also undergo mechanism-based inhibition, whereby a CYP enzyme can be completely inactivated by covalent bonding to a component of the herb. Furthermore, botanicals can elicit a biphasic cellular response, whereby CYP activity may be inhibited initially, followed by induction after prolonged incubation or repeated administration. Such factors would need to be considered in future studies in order to establish the true risk of ginseng in herb-drug interactions. 

Drugs that cause induction or inhibition of enzymes may affect the metabolism of concomitantly administered drugs, as well as of hormones and other endogenous substances. For this reason, such properties are considered undesirable, and sometimes they might constitute sufficient reason to discontinue drug development. At the very least, studies will be required to assess the magnitude of effect of likely interactions. Metabolic and toxicity studies in animals will... 

Interactions with other drugs likely to be administered concomitantly, including enzyme induction and inhibition... 

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