Rifampin metabolism

Quinolones Rifampin Nitrofurantoins Nltrolmldazoles Inhibition of synthesis or metabolism of nucleic adds... 

Maintenance doses widely vary among patients (e.g., from 1 to 20 mg/day for warfarin), and are influenced by diet (variable vitamin K intake) and medications that affect coumarin metabolism (decreased drug clearance e.g., cotrimoxazole, amiodarone, erythromycin increased clearance e.g., barbiturates, carbamaze-pine, rifampin). Thus, regular monitoring is needed... 

Rifampin, rifabutin Increase metabolism of COCs Decrease efficacy of COCs backup method of contraception is recommended... 

Elevations of serum transaminase concentrations generally are not correlated with the residual capacity of the liver to metabolize drugs, so these markers cannot be used directly as guides for residual metabolic capacity. Hepatically cleared TB drugs include isoniazid, rifampin, pyrazinamide, ethionamide, and p-aminosalicylic acid.39 Ciprofloxacin is about 50% cleared by... 

Rifampin Hepatic abnormalities monitor LFTs Reddish-orange discoloration of secretions (e.g., urine, sweat, tears) Potent inducer of CYP-mediated metabolism evaluate for drug-drug interactions... 

H. K., Eichelbaum, M., Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin, Hepatology 1996, 24, 796-801. 

Ketoconazole (a potent inhibitor of CYP3A4) has been shown to increase the oral bioavailability of cyclosporin from 22 to 56% [50]. This consisted of a 1.8-fold decrease in systemic clearance combined with a 4.9-fold decrease in oral clearance. The authors estimated that hepatic extraction was decreased only 1.15-fold, whereas the oral bioavailability increased 2.6-fold and the observation was attributed to decreased intestinal metabolism. Erythromycin was also shown to increase the oral bioavailability of cyclosporin A 1.7-fold, while pre-treatment with rifampin (an inducer of CYP3A4) decreased oral bioavailability of cyclosporin from 27% to 10% due to a 4.2-fold increase in oral clearance but only a 1.2-fold increase in systemic clearance. Floren et al. [51] have also shown that ketoconazole can double the oral bioavailability of tacrolimus in man by inhibiting gut wall CYP3A4. 

Kenny MT, Strates B Metabolism and pharmacokinetics of the antibiotic rifampin. Drug MetabRev 1981 12 159-218. 

Might antagonize verapamil Might induce hypercalcemia with thiazide diuretics Fiber laxatives (variable), oxalates, phytates, and sulfates can decrease calcium absorption if given concomitantiy Phenytoin, barbiturates, carbamazepine, rifampin increase vitamin D metabolism... 

Primary adrenal insufficiency (Addison s disease) most often involves the destruction of all regions of the adrenal cortex. There are deficiencies of cortisol, aldosterone, and the various androgens. Medications that inhibit cortisol synthesis (e.g., ketoconazole) or accelerate cortisol metabolism (e.g., phenytoin, rifampin, phenobarbital) can also cause primary adrenal insufficiency. 

Rifampin Azoles, cyclosporine, methadone propranolol, Pis, oral contraceptives, tacrolimus, warfarin Increased metabolism of other agent Avoid if possible... 

The rifamycins are a group of antibiotics of large size (Mr close to 1,000), which, among other chemical similarities, have an acetyl group at position 25. Deacetylation by carboxylesterases is a major metabolic pathway in animals and humans, as seen for example with rifampin, rifabutin, and rifalazil [97] [98],... 

Drugs that induce CYP3A4 CYP3A4 is a minor metabolizing enzyme of zaleplon. The CYP3A4-inducer rifampin reduced zaleplon C ax AUC by approximately... 

Metabolism Rifampin is metabolized in the liver by deacetylation the metabolite is still active against Mycobacterium tuberculosis. About 40% is excreted in bile and undergoes enterohepatic circulation however, the deacetylated metabolite is poorly absorbed. The half-life is approximately 3 hours after a 600 mg oral dose, up to 5.1 after a 900 mg oral dose. With repeated administration, the half-life decreases and averages approximately 2 to 3 hours. 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

Enzyme induction properties Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D. Rifampin and isoniazid have been reported to alter vitamin D metabolism. In some cases, reduced levels of circulating 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D have been accompanied by reduced serum calcium and phosphate, and elevated parathyroid hormone. 

CYP3A4 Amprenavir is metabolized by CYP3A4 and is an inhibitor (and possibly an inducer) of CYP3A4. Coadministration of fosamprenavir and drugs that induce CYP3A4, such as rifampin, may decrease amprenavir concentrations and reduce its therapeutic effect. Coadministration of fosamprenavir and drugs that inhibit CYP3A4 may increase amprenavir concentrations and increase the incidence of adverse effects. 

Because trimetrexate is metabolized by a P450 enzyme system, drugs that induce or inhibit this drug metabolizing enzyme system may elicit important drug interactions that may alter trimetrexate plasma concentrations, which include erythromycin, rifampin, rifabutin, ketoconazole, fluconazole, cimetidine, nitrogen substituted imidazole drugs (eg, clotrimazole, ketoconazole, miconazole). 

Other drugs are metabolised by Phase II synthetic reactions, catalysed typically by non-microsomal enzymes. Processes include acetylation, sulphation, glycine conjugation and methylation. Phase II reactions may be affected less frequently by ageing. Thus according to some studies, the elimination of isoniazid, rifampicin (rifampin), paracetamol (acetaminophen), valproic acid, salicylate, indomethacin, lorazepam, oxazepam, and temazepam is not altered with age. However, other studies have demonstrated a reduction in metabolism of lorazepam, paracetamol (acetaminophen), ketoprofen, naproxen, morphine, free valproic acid, and salicylate, indicating that the effect of age on conjugation reactions is variable. 

Drugs that have been associated with elevations in quinidine concentrations include acetazolamide, the antacids magnesium hydroxide and calcium carbonate, and the H2-receptor antagonist cimetidine. Cimetidine inhibits the hepatic metabolism of quinidine. Phenytoin, rifampin, and barbiturates increase the hepatic metabolism of quinidine and reduce its plasma concentrations. 

In the presence of phenytoin, the metabolism of disopyramide is increased (reducing its effective concentration) and the accumulation of its metabolites is also increased, thereby increasing the probability of anticholinergic adverse effects. Rifampin also stimulates the hepatic metaboUsm of disopyramide, reducing its plasma concentration. 

An upward adjustment in dose may be required when mexiletine is administered with phenytoin or rifampin, since these drugs stimulate the hepatic metabolism of mexiletine, reducing its plasma concentration. 

Rofecoxib is approved for the treatment of osteoarthritis, dysmenorrhea, and acute pain. The most common adverse reactions to rofecoxib are mUd to moderate GI irritation (diarrhea, nausea, vomiting, dyspepsia, abdominal pain). Lower extremity edema and hypertension occur relatively frequently (about 3.5%). It is not metabohzed by CYP2C9, so rofecoxib should not be subject to some of the interactions seen with celecoxib. However, its metabolism is increased by the coadministration of rifampin, which acts as a nonspecific inducer of hepatic metabolism. 

Other major untoward reactions are the result of rifampin s ability to induce hepatic cytochrome P-450 enzymes, leading to an increased metabolism of many drugs this action has especially complicated the treatment of tuberculosis in HIV-infected patients whose regimen includes protease inhibitors and nonnucleoside reverse transcriptase. Since rifabutin has relatively little of these effects, it is commonly substituted for rifampin in the treatment of tuberculosis in HIV-infected patients. 

Nevirapine induces and is metabolized by CYP3A4 therefore, coadministration of drugs that induce or are metabolized by this isoenzyme may result in interactions. Nevirapine may decrease the effectiveness of ethinyl estradiol-based contraceptives and can lower plasma concentrations of methadone. Nevirapine should not be administered with ketoconazole, rifampin, or rifabutin. 

Itraconazole has significant interactions with a number of commonly prescribed drugs, such as rifampin, phenytoin, and carbamazepine. Itraconazole raises serum digoxin and cyclosporine levels and may affect the metabolism of oral hypoglycemic agents and coumadin. Absorption of itraconazole is impaired by antacids, Hj blockers, proton pump inhibitors, and drugs that contain buffers, such as the antiretroviral agent didanosine. 

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