Theophylline oxidase

Heme Cytochrome c Cytochrome c oxidase, cytochrome c peroxidase, cellobiose dehydrogenase, nitrate reductase, sulphite oxidase, theophylline oxidase, cytochrome 62... 

Although many patients believe that dietary supplements will not interact with medications, recent literature suggests otherwise. Recently, many St. John s wort-drug interactions have been reported in the literature. Cases of patients developing symptoms of serotonin syndrome have been reported with St. John s wort alone and in concomitant therapy with other antidepressants such as monoamine oxidase inhibitors, serotonin reuptake inhibitors, and venlafaxine. St. John s wort may exacerbate the sedative effects of benzodiazepines, alcohol, narcotics, and other sedatives. St. John s wort may decrease the levels of protease inhibitors, cyclosporine, digoxin, and theophylline. 

Pharmacokinetic interactions Preliminary evidence suggests that Saint-John s-wort induces the cytochrome oxidase enzyme isoform CYP3A4 (Ernst 1999). This raises the potential for pharmacokinetic interactions with drugs metabolized by the same enzyme. A few cases have been reported of reduced warfarin levels (Yue et al. 2000). Similar interactions have also been reported for concurrent use with digoxin, theophylline, and cyclosporin (Nebel et al. 1999 Ruschitzka et al. 2000 Johne et al. 1999). As with any other medication, potential interactions should be considered when taking a combination of drugs. 

ALLOPURINOL BRONCHODILATORS -THEOPHYLLINE t theophylline levels Allopurinol inhibits xanthine oxidase Watch for early features of toxicity of theophylline (headache, nausea)... 

Pharmacokinetics. Absorption of xanthines after oral or rectal administration varies with the preparation used. It is generally extensive (> 95%). Caffeine metabolism varies much between individuals (t/ 2-12 h). Xanthines are metabolised (more than 90%) by numerous mixed function oxidase enzymes, and xanthine oxidase. (For further details on theophylline, see Asthma.)... 

ASA = aspirin NSAIDs = non-steroidal anti-inflammatory drugs, such as ibuprofen, naproxen, and diclofenac CNS stimulants include drugs such as pseudoephedrine, dextroamphetamine, theophylline, and caffeine MAO = monoamine oxidase CNS depressants include drugs such as benzodiazepines, barbiturates, and ethanol SSRIs = selective serotonin reuptake inhibitors, such as fluoxetine, sertraline, and paroxetine. Antidiabetic agents include drugs such as insulin, glipizide, glyburide, and metformin. 

Cytochrome c H2O2 O2 Superoxide scavenger Lactate, inhibitors of Cyt. c oxidase, theophylline (in connection with the respective substrate oxidase)... 

Theophylline and polycyclic hydrocarbons in tobacco smoke (3-methylcholanthrene) represent a second type of enzyme inducer with broad induction effects. They induce CyP lA in which no change in P4go reductase occurs and a different terminal oxidase appears. After this type of induction, the clearance of tlieophylline but not that of antipyrine is increased. These substances have served as prototypes for the classification of enzyme inducers. Obviously, when patients are on a drug with a narrow therapeutic index, their dosing regimen would need to be adjusted should a known enzyme-inducing drug be added to or deleted from their therapy. 

Umezawa et al., 1982), or with fluorescence markers (Ishimori et al., 1984). The latter system was shown to be most sensitive, the detection limit being 10-15 mol/L Double signal amplification can be obtained by inclusion of enzymes in the liposomes (Brahman et al., 1984). Thus, Haga et al. (1980) entrapped HRP in sensitized liposomes and used the liposomes to determine theophylline. The rate of HRP liberation was monitored by measuring the NADH oxidase activity of HRP with an oxygen electrode. The electrode response correlated with the theophylline concentration in the sample between 4 and 20 nmol/L... 

Stredansky M, Pizzariello A. Selective and sensitive biosensor for theophylline based on xanthine oxidase electrode. Anal Biochem 2000 285 225-9. 

Other oxidative enzymes, though certainly important in the biotransformation of some drugs (e.g., xanthine oxidase contributes to the overall metabolism of substances such as caffeine and theophylline), are not responsible for the metabolism for very many drugs compared to the GYP enzymes. 

Chemically, theophylline is 1,3-dimethylxanthine and contains both an acidic and a basic nitrogen (N-7 and N-9, respectively). Physiologically, it behaves as an acid (pKa = 8.6), and its poor aqueous solubility can be enhanced by salt formation with organic bases. Theophylline is metabolized by a combination of C-8 oxidation and N-demethylation to yield methyluric acid metabolites (Fig. 44.20). The major urinary metabolite is 1,3-dimethyl uric acid, which is the product of the action of xanthine oxidase. Beoause none of the metabolites is uric acid itself. 

Hepatic metabolism is predominantly mediated via the cytochrome P-450 (CYP) isoenzymes CYP2E1 and CYP3A4 (8-hydroxylation to 1,3-dimethyluric acid, 40 to 50%), and CYP1A2 (A-demethylation to 3-methylxanthine, 10 to 15%, and 1-methylxanthine). 1-Methylxanthine is further oxidized, by xanthine oxidase, to 1-methyluric acid (15 to 20%). " Caffeine and 3-methylxanthine are the only theophylline metabolites with pharmacological activity, but only... 

Berkowitz Spector S, Pool W. The interaction of caffeine, theophylline and theobrcmine with monoamine oxidase inhibitora. EurJ Pharmacol (1911 ) 16,315-21. 

Uncertain. Allopurinol, a xanthine oxidase inhibitor, can block the conversion of methylxanthine to methylurie aeid, but this had no effeet on theophylline levels in two studies. One suggestion is that allopurinol inhibits the oxidative metabolism of theophylline by the liver. ... 

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