Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D06103 (Theophylline)
 2,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of cyclic 3'5'-adenosine monophosphate (cAMP), adrenalin and theophylline on interferon synthesis induced by influenza B virus (Lee strain) in chick embryo cell cultures was studied. In 5-day-old cell culture, theophylline was shown to enhance the inhibiting effect of exogenous cAMP and adrenalin on interferon synthesis and in 1-day-old culture, on the contrary, to enhance interferon production whereas adrenaline under these conditions had no effect on interferon synthesis at all. In 5-day-old cultures the activity of adrenalin and theophylline was manifested when they were added to the maintenance medium not later than 4 hours postinfection, and was not associated with the influence on interferon inducer adsorption on to cells or on virus multiplication in sensitive systems. Treatment of cells with these substances had no effect on interferon release from the cells. In the concentration used, adrenalin and theophylline exerted no cytotoxic effect. Theophylline inhibited incorporation of 3H-uridine and 14C-leucine into the acid insoluble fraction of the infected cells in 1-day-old cultures, while in 5-day-old cultures this was observed only when adrenalin and theophylline were used together. It is suggested that endogenous cAMP is essential for control of interferon synthesis and that different cAMP levels in cells of different ages may be one of the causes of the varying potency for interferon synthesis in young and old cell cultures.
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PMID:The influence of substances changing the intracellular concentration of cyclic adenosine 3'5'-monophosphate on interferon synthesis in chick embryo cell culture. 17 27

Chronic obstructive pulmonary disease (COPD) is the fifth commonest cause of death in North America and is the only leading cause of death that is increasing in prevalence. Early detection and prevention through smoking cessation are essential to stem this epidemic. Once COPD is diagnosed there is a compelling rationale for vaccination against influenza and possibly pneumococcal pneumonia, although proof of efficacy is lacking. If airways obstruction is present, inhaled quaternary anticholinergic bronchodilators or inhaled beta 2 agonists or both may be of benefit, the former agents showing fewer side effects and often greater efficacy in elderly patients. Theophylline may enhance the effect or increase the duration of the bronchodilatation produced by an inhaled agent and may offer added nonbronchodilatory effects such as improved respiratory muscle endurance and ventilatory stimulation. If significant airflow obstruction persists, an objectively monitored trial of oral steroid therapy is required. Limitation of activity despite optimum medical therapy may be alleviated in selected patients by a supervised exercise rehabilitation program. If hypoxemia is present supplemental oxygen therapy will improve the patient's survival and quality of life. Additional therapies, from respiratory stimulants to lung transplantation, remain under investigation.
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PMID:Guidelines for the assessment and management of chronic obstructive pulmonary disease. Canadian Thoracic Society Workshop Group. 149 54

Many drugs have been found to increase or decrease the clearance of theophylline, probably by interaction with one or more of the variants of the cytochrome P450 drug-metabolising system. Theophylline may be particularly susceptible to alteration of its clearance because of the particular form(s) of the P450 system involved, because its metabolism is saturable, and/or because 90% of its elimination is via metabolism. Its clearance has been found to be decreased (typically by around 25%, but often by far more) by erythromycin, troleandomycin (triacetyloleandomycin), roxithromycin, enoxacin, ciprofloxacin, pefloxacin, norfloxacin, ofloxacin, fluoroquinolone T-3262, pipemidic acid, cimetidine, etintidine, propranolol, verapamil, diltiazem, nifedipine, furosemide (frusemide), at least some anovulent agents, viloxazine, allopurinol, ticlopidine, idrocilamide, thiabendazole, disulfiram, influenza- and BCG-vaccination, interferon, and caffeine (half-life increase). In contrast, theophylline clearance (clearance/bioavailability) was found to be increased by isoprenaline (isoproterenol), terbutaline, some corticosteroids, phenytoin, phenobarbital, activated charcoal, felodipine moricizine, benzodiazepines and sulfinpyrazone - typically by about 25%, but sometimes by as much as 80% or more. For several of these concomitant medications, however, only some of the published studies can substantiate an influence, which may highlight the sensitivity of some interactions to particular experimental and/or clinical conditions, e.g. with terbutaline, erythromycin, ciprofloxacin, norfloxacin, ofloxacin, phenobarbital, cimetidine, verapamil, diltiazem, nifedipine, anovulents, allopurinol and influenza vaccination. Moreover, reports both of inhibition and of induction of theophylline clearance by each of rifampicin and isoniazid have appeared. Nevertheless, under investigation many medications have not been found to perceptibly influence theophylline disposition kinetics, e.g. ephedrine, orciprenaline (metaproterenol), prednisone, prednisolone, temelastine, terfenadine, mequitazine, picumast, repirinast, josamycin, midecamycin, miocamycin, spiramycin, amoxicillin, ampicillin, cefalexin, cefaclor, ceftibuten, cotrimoxazole (trimethoprim plus sulfamethoxazole), tetracycline, doxycycline, lomefloxacin, fluoroquinolones NY-198 and AM-833, nalidixic acid, lincomycin, metronidazole, certain antacids, ranitidine, roxatidine, pirenzepine, rioprostil, metoclopramide, metoprolol, atenolol, nadolol, medroxyprogesterone, dextropropoxyphene (propoxyphene), piroxicam, ozagrel, mebendazole and ascorbic acid.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacokinetic interactions between theophylline and other medication (Part I). 167 42

The effect of influenza vaccination on steady-state pharmacokinetics of theophylline was studied in six healthy young adults by comparing pharmacokinetic parameters found on days 4 and 5 during a 5-day course of theophylline alone with those obtained after influenza vaccination on day 4 of a second study phase. Theophylline plasma concentrations were measured by means of high-pressure liquid chromatography (HPLC) analysis and, in part, with a manual ultraviolet spectrophotometric method and with an EMIT assay. On the fourth and fifth days of each of the two periods of drug administration, theophylline plasma concentration-time curves were evaluated, and the following pharmacokinetic parameters were compared: trough plasma concentration (cmin), peak plasma concentration (cmax), time to peak (tmax), and the area under the curve during a dosing interval (AUC). None of these pharmacokinetic parameters of theophylline before and after vaccination were found to be significantly different with any of the analytical methods.
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PMID:No effect of influenza vaccination on theophylline pharmacokinetics as studied by ultraviolet spectrophotometry, HPLC, and EMIT assay methods. 305 38

Experimental and more limited clinical studies have suggested that influenza vaccination may depress the oxidative hepatic metabolism of various drugs and lead to drug toxicity. The alleged mechanism is the formation of interferon and the resulting decrease in cytochrome P-450 available for drug oxidation. Because of the clinical and basic science implications of these reports, we undertook to study the effects of influenza vaccine on the metabolism of three commonly used drugs: chlordiazepoxide, theophylline, and lorazepam. Our healthy male subjects were studied just before and 1 and 7 days after vaccination. As expected, lorazepam metabolism, which proceeds by glucuronidation and not oxidation, was not altered by vaccination. Surprisingly, however, the oxidation of chlordiazepoxide was also not depressed by the vaccine. Theophylline oxidation, which proceeds primarily by microsomal oxidation (demethylation), was significantly decreased 1 day, but not 7 days, after vaccination. Serum alpha-interferon levels rose after vaccination for only about 8 hours, and levels of gamma-interferon rose to about 500 IU/ml at 24 hours, peaked at 72 hours, and returned to normal by 100 hours after dosing. It appeared that the higher the theophylline clearance before vaccination, the greater the degree of clearance depression after vaccination. Thus the inhibition of drug oxidation after influenza vaccination is selective and each drug should be studied individually. The degree of depression of theophylline clearance is small and transient and appears to be greater in subjects with higher prevaccination clearance.
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PMID:Effects of influenza virus vaccine on hepatic drug metabolism. 397 1

Total Theophylline clearance rate was measured before and 24 hours after standard influenza vaccination in seven men with stable chronic obstructive lung disease. In four, total theophylline clearance rate was also measured 48 hours after vaccine administration. There was no significant change in the clearance rate after either time interval. These results do not support recent recommendations to monitor serum theophylline concentrations or reduce theophylline dosage during the 48-hour period following influenza vaccination. Nevertheless, pending further studies, patients maintained on a regimen of theophylline preparations should be followed clinically for theophylline toxicity for the first several days after receiving influenza vaccine.
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PMID:Influenza vaccination and theophylline pharmacokinetics in patients with chronic obstructive lung disease. 665 88

Rifampin and rifabutin induce the metabolism of many drugs, which may result in subtherapeutic concentrations and failure of therapy. However, differences between rifabutin and rifampin in potency of induction, and the specific enzymes which are altered, are not clear. This study, involving 12 adult male volunteers, compared the effects of 14-day courses of rifampin and rifabutin on clearance of theophylline, a substrate for the hepatic microsomal enzyme CYP1A2. Subjects were given oral theophylline solution (5 mg/kg of body weight) on day 1 and then randomized to receive daily rifampin (300 mg) or rifabutin (300 mg) on days 3 to 16. Theophylline was readministered as described above on day 15. The first treatment sequence was followed by a 2-week washout period; subjects then received the alternative treatment. Theophylline concentrations were determined for 46 h after each dose, and pharmacokinetic parameters were determined. One subject developed flu-like symptoms while taking rifabutin and withdrew voluntarily. Results from the remaining 11 subjects are reported. Compared with the baseline, the mean area under the concentration-time curve (AUC) (+/- standard deviation) for theophylline declined significantly following rifampin treatment (from 140 +/- 37 to 100 +/- 24 micrograms . h/ml, P <0.001); there was no significant change following rifabutin treatment (136 +/- 48 to 128 +/- 45 micrograms.h/ml). Baseline theophylline AUCs before each treatment phase were not different. A comparison of equal doses of rifampin and rifabutin administered to healthy volunteers for 2 weeks indicates that induction of CYP1A2, as measured by theophylline clearance, is significantly less following rifabutin treatment than it is following rifampin treatment. However, the relative induction potency for other metabolic enzymes remains to be investigated.
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PMID:Induction of theophylline clearance by rifampin and rifabutin in healthy male volunteers. 884 95

Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthem subitum. It occurs worldwide, but is most prevalent in East Asia, and every year several hundreds of Japanese children are affected by influenza-associated encephalopathy. Mortality has recently declined, but is still high. Many survivors are left with motor and intellectual disabilities, and some with epilepsy. This article reviews various syndromes of acute encephalopathy by classifying them into three major categories. The first group caused by metabolic derangement consists of various inherited metabolic disorders and the classical Reye syndrome. Salicylate is a risk factor of the latter condition. The second group, characterized by a systemic cytokine storm and vasogenic brain edema, includes Reye-like syndrome, hemorrhagic shock and encephalopathy syndrome, and acute necrotizing encephalopathy. Non-steroidal anti-inflammatory drugs, such as diclofenac sodium and mephenamic acid, may aggravate these syndromes. Severe cases are complicated by multiple organ failure and disseminated intravascular coagulation. Mortality is high, although methylprednisolone pulse therapy may be beneficial in some cases. The third group, characterized by localized edema of the cerebral cortex, has recently been termed acute encephalopathy with febrile convulsive status epilepticus, and includes hemiconvulsion-hemiplegia syndrome and acute infantile encephalopathy predominantly affecting the frontal lobes. Theophylline is a risk factor of these syndromes. The pathogenesis is yet to be clarified, but an increasing body of evidence points to excitotoxicity and delayed neuronal death.
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PMID:Acute encephalopathy associated with influenza and other viral infections. 1736 76

Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthem subitum. It occurs worldwide, but is most prevalent in East Asia, and every year several hundreds of Japanese children are affected by influenza-associated encephalopathy. Mortality has recently declined, but is still high. Many survivors are left with motor and intellectual disabilities, and some with epilepsy. This article reviews various syndromes of acute encephalopathy by classifying them into three major categories. The first group caused by metabolic derangement consists of various inherited metabolic disorders and the classical Reye syndrome. Salicylate is a risk factor of the latter condition. The second group, characterized by a systemic cytokine storm and vasogenic brain edema, includes Reye-like syndrome, hemorrhagic shock and encephalopathy syndrome, and acute necrotizing encephalopathy. Non-steroidal anti-inflammatory drugs, such as diclofenac sodium and mephenamic acid, may aggravate these syndromes. Severe cases are complicated by multiple organ failure and disseminated intravascular coagulation. Mortality is high, although methylprednisolone pulse therapy may be beneficial in some cases. The third group, characterized by localized edema of the cerebral cortex, has recently been termed acute encephalopathy with febrile convulsive status epilepticus, and includes hemiconvulsion-hemiplegia syndrome and acute infantile encephalopathy predominantly affecting the frontal lobes. Theophylline is a risk factor of these syndromes. The pathogenesis is yet to be clarified, but an increasing body of evidence points to excitotoxicity and delayed neuronal death.
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PMID:Acute encephalopathy associated with influenza and other viral infections. 1778 37