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)

Rifampin is a potent inducer of cytochrome P-450 oxidative enzymes. A few examples of well-documented clinically significant interactions include interactions with warfarin, oral contraceptives, cyclosporine, glucocorticoids, ketoconazole or itraconazole, theophylline, quinidine sulfate, digitoxin or digoxin, verapamil hydrochloride, human immunodeficiency virus-related protease inhibitors, zidovudine, delavirdine mesylate, nifedipine, and midazolam. Recent reports have demonstrated clinically relevant interactions with numerous other drugs, such as buspirone hydrochloride, zolpidem tartrate, simvastatin, propafenone hydrochloride, tacrolimus, ondansetron hydrochloride, and opiates. Rifabutin reduces serum concentrations of antiretroviral agents, but less so than rifampin. To avoid a reduced therapeutic response, therapeutic failure, or toxic reactions when rifampin is added to or discontinued from medication regimens, clinicians need to be cognizant of these interactions. Enhanced knowledge of known interactions will continue to develop, including research on the induction of specific cytochrome P-450 isoenzymes and on the importance of the P-glycoprotein transport system. New rifampin and rifabutin interactions will be discovered with further investigations.
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PMID:Rifampin and rifabutin drug interactions: an update. 1199 7

Rifampin is a potent inducer of cytochrome P-450 oxidative enzymes as well as the P-glycoprotein transport system. Several examples of well-documented clinically significant interactions include warfarin, oral contraceptives, cyclosporine, itraconazole, digoxin, verapamil, nifedipine, simvastatin, midazolam, and human immunodeficiency virus-related protease inhibitors. Rifabutin reduces serum concentrations of antiretroviral agents, but less so than rifampin. Examples of clinically relevant interactions demonstrated by recent reports include everolimus, atorvastatin, rosiglitazone/pioglitazone, celecoxib, clarithromycin, caspofungin, and lorazepam. To avoid a decreased therapeutic response, therapeutic failure, or toxic reactions when rifampin is added to or discontinued from medication regimens, clinicians need to be cognizant of these interactions. Studies and cases of rifampin drug interactions continue to increase rapidly. This review is a timely reminder to clinicians to be vigilant.
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PMID:Update on rifampin and rifabutin drug interactions. 1827 21

Tuberculosis (TB) and HIV continue to be two of the major causes of morbidity and mortality in the world, and together are responsible for the death of millions of people every year. There is overwhelming evidence to recommend that patients with TB and HIV co-infection should receive concomitant therapy of both conditions regardless of the CD4 cell count level. The principles for treatment of active TB disease in HIV-infected patients are the same as in HIV-uninfected patients. However, concomitant treatment of both conditions is complex, mainly due to significant drug-drug interactions between TB and HIV drugs. Rifamycins are potent inducers of the cytochrome P450 (CYP) pathway, leading to reduced (frequently sub-therapeutic) plasma concentrations of some classes of antiretrovirals. Rifampicin is also an inducer of the uridine diphosphate glucuronosyltransferase (UGT) 1A1 enzymes and interferes with drugs, such as integrase inhibitors, that are metabolized by this metabolic pathway. Rifampicin is also an inducer of the adenosine triphosphate (ATP) binding cassette transporter P-glycoprotein, which may also lead to decreased bioavailability of concomitantly administered antiretrovirals. On the other side, rifabutin concentrations are affected by the antiretrovirals that induce or inhibit CYP enzymes. In this review, the pharmacokinetic interactions, and the relevant clinical consequences, of the rifamycins-rifampicin, rifabutin, and rifapentine-with antiretroviral drugs are reviewed and discussed. A rifampicin-based antitubercular regimen and an efavirenz-based antiretroviral regimen is the first choice for treatment of TB/HIV co-infected patients. Rifabutin is the preferred rifamycin to use in HIV-infected patients on a protease inhibitor-based regimen; however, the dose of rifabutin needs to be reduced to 150 mg daily. More information is required to select optimal treatment regimens for TB/HIV co-infected patients whenever efavirenz cannot be used and rifabutin is not available. Despite significant pharmacokinetic interactions between antiretrovirals and antitubercular drugs, adequate clinical response of both infections can be achieved with an acceptable safety profile when the pharmacological characteristics of drugs are known, and appropriate combination regimens, dosing, and timing of initiation are used. However, more clinical research is needed for newer drugs, such as rifapentine and the recently introduced integrase inhibitor antiretrovirals, and for specific population groups, such as children, pregnant women, and patients affected by multidrug-resistant TB.
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PMID:Treatment optimization in patients co-infected with HIV and Mycobacterium tuberculosis infections: focus on drug-drug interactions with rifamycins. 2477 31