Theophylline ethanolate

Theophylline ethanolate of piperazine (CADIPEIYLLATE) iii. Anticholinergics 250-500 mg/day oral/IV... 

Most cases of poisoning are treated conservatively, i.e. the symptoms arc treated and the drug is eliminated by nonnal metabolism and renal excretion. When there is hepatic or renal insufficiency, active measures such as haemodialysis or charcoal haemoperfusion may be attempted.. Such measures are normally restricted to a small group of drugs and poisons including salicylate, phenobarbitone. theophylline, ethanol, methanol, ethylene glycol and lithium. Where active measures are used to eliminate drugs, plasma concentrations should be monitored. 

Low antiepileptic drug levels, drug overdose (e.g., cocaine, isoniazid, theophylline, phenothiazine), ethanol-related, and drug withdrawal... 

Liver metabolism is affected by methylxanthines. In high doses, theophylline and caffeine increase the level of cyclic AMP. Very high levels of methylxanthines decrease the level of branched chain and aromatic amino acids in plasma. Coffee appears to have little effect on ethanol metabolism. 

Materials. Tetrahydrofuran (THF) was freshly distilled from sodium, and triethylamine from P2O5. Methacryloyl chloride (Aldrich Chemical Co.) and NJV-dimethylacrylamide (DMAAm), (Aldrich Chemical Co.) were distilled under reduced pressure prior to use. 2,2 -Azobisisobutyronitrile (AIBN) (Eastman Kodak) and theophylline (Mp 275 °C) (Aldrich Chemical Co.) were recrystallized from methanol and water, respectively. Hexanes, /i-heptane, and ethanol were used as received. 

Examples of solvent-mediated transformation monitoring include the conversion of anhydrous citric acid to the monohydrate form in water [235,236], CBZ with water [237] and ethanol-water mixtures [238,239], and cocrystallization studies of CBZ, caffeine, and theophylline with water [240]. Raman spectroscopy was used to monitor the crystallization rate and solute and solvent concentrations as griseofulvin was removed from an acetone solution using supercritical CO2 as an antisolvent [241]. Progesterone s crystallization profile was monitored as antisolvent was added [242]. 

Syntheses of xanthines, uracUs and related compounds from the corresponding a-hninooxime derivatives were described For example, oxime ester 134 in refluxing ethanol afforded theophyllin 135 in good yield (equation 59) . ... 

The sodium salt of theophylline was obtained as follows to a solution of 36.34 g (0.2 mol) of theophylline in 120 mL of 50% aqueous ethanol at 80 C was added 50 mL (0.2 mol) of aqueous 4 N sodium hydroxide. Chilling to 0°C, filtration of the precipitate, washing with 50 mL of 96% ethanol, then with 100 mL ether, and drying in a vacuum desiccator over phosphorus pentoxide provides 28.0 g of the anhydrous salt. 

Conversion of L-fucosyl- and 3 -0-methyl-D-glycosyl-purines into nucleosides of two naturally occurring, rare sugars, 6-deoxy-L-talose and 3-O-methyl-D-mannose, could be achieved57 by stereospecific reduction at C-2 of 7-(6-deoxy-3,4-0-isopropylidene-/ -L-h/xo-hexopyranosyl-2-ulose)theophylline (35a) and 7-(4,6-0-benzylidene-3-0-methyl-/ -D-orobtno-hexopyranosyI-2-ulose)theophylline (8). Treatment of 35a and 8 with sodium borohydride in ethanol afforded the expected 7-(6-deoxy-3,4-0-isopropylidene-/ -L-talopyranosyI)theophylline (84) and 7-(4,6-... 

The separation of cimetidine and its metabolites is usually carried out by extraction of the biological medium with 1-octanol fran an aqueous alkaline pH solution followed by mixing, addition of an internal standard and centrifugation. The extraction with octanol is repeated and the combined extracts are re-extracted with dilute hydrochloric acid. The aqueous acid solution is then separated, ethanol is added and mixed. This is then followed by saturating the mixture with a large amount of potassium or sodium carbonate to "salt out" the ethanol layer which contains the cimetidine and its metabolite, the sulfoxide. Several different internal standards have been used Metiamide, 1-methyl-3-[2-[[(5-methyl-imidazole-4-yl) -methyl] thio]ethyl]-2-thiourea,19 31 39 (N-cyano-N1-methy1-N"-(3-(4-imidazolyl)-propyl)guanidine32, and 13-hydroxy-theophylline. 0 After extraction the samples are either evaporated to dryness and reconstituted with a known amount of ethanol, injected directly or dissolved in the mobile phase for the HPLC analysis. 

A solution of 10.0 g of l-bromohexanone-5 in 100 ml of ethanol was gradually mixed at the boil with vigorous stirring with 11.3 g of the sodium salt of theophylline in 100 ml of water. After 3 hours refluxing the alcohol was distilled off, and the residual aqueous phase was cooled and made alkaline and extracted with chloroform. The chloroform solution was evaporated and the residue re-crystallized from a little isopropanol to yield 7-(5-oxohexyl) theophylline. MP 75°-76°C a yield of about 80% (calculated on the reacted theophylline). 

A solution of 100 g of theophylline in 500 ml 1 M solution of KOH was prepared potassium theophylline. To that potassium theophylline was added 120 ml monochlorhydrin ethylene glycol, a mixture was heated at 130°C for 4 hours. The product was dissolved in ethanol and filtered. After crystallization was obtained 7-(2-hydroxyethyl)theophylline. 

Jusko WJ, Gardner MJ, Mangione A, Schentag JJ, Koup JR, Vance JW. Factors affecting theophylline clearances Age, tobacco, marijuana, cirrhosis, congestive heart failure, obesity, oral contraceptives, benzodiazepines, barbiturates, and ethanol. J Pharm Sci 1979 68 1358-66. 

Heating 5-(benzylideneamino)-l,3-dimethyluracil-6-amine, which is readily available by the condensation of l,3-dimethyluracil-5,6-diamine with benzaldehyde in ethanol, °° with thionyl chloride affords 8-phenyltheophyllinc (7, R = Ph) in good yield. This reaction is applicable to other 5-(arylideneamino)-l,3-dimethyluracil-5,6-diamines to give the corresponding 8-substi-tuted theophyllines 7. ... 

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. 

It is important to realize that a discussion of solvent polarity is only useful when considered in relation to a particular solute. Thus, for a semipolar solute such as theophylline, pure ethanol might be considered nonpolar, but for a relatively non-polar solute such as hydrocortisone, ethanol might be considered semipolar. This concept is illustrated in Fig. 1. For nonpolar and polar solutes, solubility will continually decrease or increase, respectively, as solvent polarity increases. For semipolar solutes, solubility reaches a maximum at some intermediate solvent polarity. It should be noted that the reverse argument (i.e., solute polarity should be discussed relative to solvent polarity) is also valid. 

Skin disinfection before insertion of peripheral infusion catheters is standard practice. Ethanol 70% has been compared with 2% iodine dissolved in 70% ethanol in a prospective, randomized trial in 109 patients who were given infusions of prednisone and theophylline (2). Phlebitis occurred six times in the ethanol group and 12 times in the iodine group. The relative risk reduction of 53% failed to reach significance, but the power of the study was only 0.55, so there was a 45% chance of missing a true difference. As vast numbers of catheters are inserted each year, a small difference in phlebitis rate could save many patients discomfort. 

Christensen JM, Suvanakoot U, Ayres JW, Tavipatana W. Ethyl lactate-ethanol-water cosolvent for Intravenous theophylline. Res Commun Chem Pathol Pharmacol 1985 50(1) 147-150. 

Oxidative reactions catalysed by non-microsomal enzymes are less varied than those mediated by cytochrome P450 mono-oxygenases but are important in the metabolism of some drugs (e.g. isoproterenol, methylxanthines, methimazole, ethanol, chloral hydrate), endogenous substances (adrenalin, histamine) and naturally occurring compounds (vitamin A). Theophylline and caffeine (methylxanthines) simultaneously undergo microsomal cytochrome... 

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