Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The presence of cytochrome P450 enzymes in the small bowel results in the reduced bioavailability of several drugs. Recently, there has been much research on the interplay between these enzymes and transporter proteins such as P-glycoprotein. Intestinal drug metabolism not only has an effect on drug disposition but also may have a role in protecting the host from xenobiotics. Although there is some information on how both the enzymes and transporters develop in the small bowel with age, there is little information regarding the clinical effects of these changes. In addition to developmental changes, the influence of gastrointestinal disease and nutrition are additional covariates in the intestinal metabolism of drugs.
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PMID:Intestinal metabolism and transport of drugs in children: the effects of age and disease. 1860 62

Digoxin has a narrow therapeutic margin and potentially life-threatening cardiac adverse effects. Gastrointestinal disorders, neuropsychological disorders and bradycardia are warning signs. Some drug combinations can aggravate the cardiac adverse effects of digoxin, or reduce its efficacy. We reviewed the literature, using the standard Prescrire methodology, in order to examine which drugs are involved in these interactions, and the mechanisms involved. Most relevant data are based on small pharmacokinetic studies or detailed case reports. The adverse effects of digoxin are potentiated by renal impairment, which may be pre-existing or due to nephrotoxic drugs such as nonsteroidal antiinflammatory drugs (NSAIDs), angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor antagonists and ciclosporin. Some coadministered drugs such as macrolides and cardiovascular drugs (especially amiodarone) can cause digoxin overdose through pharmacokinetic interactions. The mechanism most often implicated is inhibition of P-glycoprotein, of which digoxin is a substrate. Hypercalcaemia and hypokalaemia inducing drugs, heart-rate lowering drugs, and drugs that prolong the QT interval or slow cardiac conduction can potentiate the cardiac adverse effects of digoxin. Plasma concentration of digoxin is not affected. Several drugs, including sucralfate, acarbose, cytotoxic agents, and enzyme inducers, can reduce digoxin plasma concentrations. This effect is attributed to decreased gastrointestinal absorption or increased elimination of digoxin. In practice, patients treated with digoxin, and their caregivers, should be aware that digoxin has a narrow therapeutic margin and frequent and potentially severe adverse effects. Close clinical monitoring is necessary to detect early warning signs (bradycardia and gastrointestinal or neurological disorders). Digoxin assay alone is not always sufficient. Special care is required for patients with renal failure, the elderly and patients receiving potentially interacting drugs.
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PMID:Digoxin: serious drug interactions. 2056 89