Cytochrome P450 isoenzymes drug metabolism

Unclear. An in vitro study found that tacrolimus and theophylline each exhibited a negligible effect on the metabolism of the other drug. However, the authors of the case report suggest that theophylline levels in their patient could have been sufficient to inhibit the cytochrome P450 isoenzyme-mediated metabolism of tacrolimus. ... 

By using in vitro preparations of human enzymes it is possible to predict those antibiotics that will adversely affect the metabolism of other drugs [110]. Such studies have shown that rifaximin, at concentrations ranging from 2 to 200 ng/ml, did not inhibit human hepatic cytochrome P450 isoenzymes 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1 and 3A4 [34], In an in vitro hepatocyte induction model, rifaximin was shown to induce cytochrome P450 3A4 (CYP3A4) [34], an isoenzyme which rifampicin is known to induce [109],... 

Changes in protein binding Changes in hepatic enzymes and drug metabolism (e.g., hepatic cytochrome P450 isoenzymes)... 

Acceptable drug metabolism and interaction profiles based on microsomal and recombinantly expressed cytochrome P450 isoenzyme studies Recent addition Toxicogenomic data for early assessment of alteration in expression of RNA transcripts (and therefore proteins) related to toxic responses so that modification of safer and more potent variants of NME could be made and identified early... 

Zaleplon is primarily metabolized by aldehyde oxidase and use with inhibitors of this enzyme, such as cimetidine, may result in increased plasma concentrations of zaleplon. Zaleplon is also partly metabolized by the cytochrome P450 isoenzyme CYP3A4 and, consequently, caution is advised when zaleplon is given with drugs that are substrates for, or potent inhibitors of, this isoenzyme. Cimetidine is also an inhibitor of CYP3A4 and thus inhibits both the primary and secondary metabolic pathways of zaleplon. Use with rifampicin or other potent enzyme-inducing drugs may accelerate the metabolism of zaleplon and reduce its plasma concentrations [40]. 

Cimetidine is an inhibitor of several cytochrome P450 isoenzymes and so potentiates a large number of drugs ordinarily metabolised by that system, notably, theophylline, warfarin, phenytoin and propranolol. Depending on the interacting drug, up to 50% inhibition of metabolism may occur when cimetidine 2000 mg/d is taken. 

Erythromycin inhibits a cytochrome P450 isoenzyme and impairs the metabolism of theophylline, warfarin, carbamazepine and methylprednisolone. The mean reduction in drug clearance is 20-25%. 

Interactions. Drugs that lower gastric acidity, e.g. antacids, histamine H2 receptor antagonists, impair the absorption of ketoconazole from the gastrointestinal tract. Like all imidazoles, ketoconazole binds strongly to several cytochrome P450 isoenzymes and thus inhibits the metabolism (and increases effects of) oral anticoagulants, phenytoin and cyclosporin, and increases the risk of cardiac arrhythmias with terfenadine. A disulfiram-like reaction occurs with alcohol. Concurrent use of rifampicin, by enzyme induction of CYP 3A, markedly reduces the plasma concentration of ketoconazole. 

Paclitaxel is metabolized by the cytochrome P450 isoenzymes CYP2C and CYP3A4 (53), and drugs that inhibit or induce these isozymes would be expected to alter the metabolism of paclitaxel. In vitro ranitidine, diphenhydramine, vincristine, vinblastine, and doxorubicin had little or no effect on the metabolism of paclitaxel, but... 

Studies have been conducted in animals to attempt to clarify the role of varying rates of drug metabolism in humans and animals and the likelihood for development of addiction/dependence to narcotics. Hydromorphone has been studied in several animal models because it is metabolized in humans by specific cytochrome P450 isoenzymes. So far, studies have looked at administration of agents that either block or promote P450 isoenzymes responsible for hydrocodone metabolism and the impact of enhanced or degraded metabolism of hydrocodone on those animal models. Results in rats and rhesus monkeys have demonstrated little effect from modifying hydrocodone metabolism. 

Polymorphisms also exist for specific isoenzymes of cytochrome P450. For example, there is a polymorphism within the human population for a cytochrome P450 isoenzyme that catalyzes the 4-hyroxylation of the drug debrisoquine. Extensive metabolizers hydroxylate this drug 10-200 times faster than poor metabolizers . Poor metabolizers express much less of the isoenzyme involved in this reaction than extensive metabolizers. This polymorphism also appears to affect the metabolism of environmental agents. For example, there appears to be an association between the poor-metabolizer phenotype and Parkinson s disease. By contrast, the extensive-metabolizer phenotype may be correlated with an increased risk of developing cancer. 

In vitro studies KOI Cynthia Wenner/ Bastyr University Investigate the correlation between formulation composition and bioactivity of echinacea Study herb/drug interactions by examining echinacea s effects on drug-induced inhibition of Cytochrome P450 isoenzymes involved in drug metabolism... 

I Drug-Drug Interactions. Carbamazepine induces the hepatic cytochrome P450 isoenzymes (1A2, 3A4, 2C9/10, and 2D6), which increases the metabolism of many medications, such as anticonvulsants (i.e., lamotrigine, topiramate, and valproate), antidepressants (i.e., tricyclics and bupropion), antipsychotics (i.e., clozapine, haloperi-dol, fluphenazine, olanzapine, and thiothixene), benzodiazepines, oral contraceptives, and protease inhibitors. " Women who receive carbamazepine require higher dosages of oral contraceptives or alternative contraceptive methods." ... 

Donepezil is metabolized by isoenzymes 2D6 and 3A4 of hepatic cytochrome P450. The drug may then be glucuronidated. Excretion is primarily renal, with some unchanged drug detectable in the urine. Excretion may also occur through the bile and feces. 

No. Chemical substances present in grapefruit juice inhibit cytochrome P450 isoenzymes involved in amlodipine metabolism. These substances decrease the first-pass metabolism of the drug and increase serum concentrations. 

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