Theophylline Dyphylline

As shown below, theophylline is 1,3-dimethylxanthine theobromine is 3,7-dimethylxanthine and caffeine is 1,3,7-trimethylxanthine. A theophylline preparation commonly used for therapeutic purposes is aminophylline, a theophylline-ethylenediamine complex. A synthetic analog of theophylline (dyphylline) is both less potent and shorter-acting than theophylline. The pharmacokinetics of theophylline are discussed below (see Clinical Use of Methylxanthines). The metabolic products, partially demethylated xanthines (not uric acid), are excreted in the urine. 

Ou, C.-N. Frawley, V.L. Theophylline, dyphylline, caffeine, acetaminophen, sedicylate, acetylsaUcylate, procainamide, and N-acetylprocainamide determined in serum with a single Uquid-chromatographic assay. Clin.Chem., 1982, 28, 2157-2160... 

Dilor-G Tablets—dyphylline, guaifenesin Dyflex-G Tablets—dyphylline, guaifenesin Glyceryl-T Liquid—theophylline, guaifenesin Hydrophed Tablets—theophylline, hydroxyzine, ephedrine sulfate... 

DYPHYLLINE Dyphylline is a derivative of theophylline it is not a theophylline salt, and is not metabolized to theophylline in vivo. Although dyphylline is 70% theophylline by molecular weight ratio, the amount of dyphylline equivalent to a given amount of theophylline is not known. Specific dyphylline serum levels may be used to monitor therapy serum theophylline levels will not measure dyphylline. The minimal effective therapeutic concentration is 12 mcg/mL. 

Dyphylline- Dyphylline, a chemical derivative of theophylline, is not a theophylline salt as are the other agents. It is about one-tenth as potent as... 

The following agents may be affected by theophylline Benzodiazepines, -agonists, halothane, ketamine, lithium, nondepolarizing muscle relaxants, propofol, ranitidine, and tetracyclines. Probenecid may increase the effects of dyphylline. 

Temazepam (Restoril) [C-IV] [Sedative/Hypnotic/ Benzodiazepine] Uses Insomnia, anxiety, depression, panic attacks Action Benzodiaz ine Dose 15-30 mg PO hs PRN X in elderly Caution [X, /-] Potentiates CNS dqjressive effects of opioids, barbs, EtOH, antihistamines, MAOIs, TCAs Contra NAG Disp Caps SE Confusion, dizziness, drowsiness, hangover Interactions T Effects W/ cimetidine, disulfiram, kava kava, valerian T CNS depression W/ anticonvulsants, CNS depressants, EtOH t effects OF haloperidol, phenytoin X effects W/ aminophylline, dyphylline, OCPs, oxtriphylline, rifampin, theophylline, tobacco X effects OF levodopa EMS Use caution w/ other benzodiazepines, antihistamines, opioids and verapamil, can T CNS depression concurrent EtOH can T CNS depression abruptly D/C after >10 d use may cause withdrawal OD May cause profound CNS depression, confusion, bradycardia, hypotension, and altered reflexes flumazenil can be used as antidote, activated charcoal may be effective... 

Though better tolerated, significantly less bronchodilating activity vs theophylline. Serious dosing errors possible if dyphylline monitored with theophylline serum assays... 

Oral sustained-release, 24 hours 100, 200, 300 mg tablets and capsules 400, 600 mg tablets Parenteral 200, 400, 800 mg/container, theophylline and 5% dextrose for injection Other Methylxanthines Dyphylline (generic, other)... 

No interference was seen with the following drugs (no concentrations have been stated in the literature) clemastine, chlorpheniramine, codeine, dextromethorphan, diaphenhydramine, dyphylline, isoproterenol, phenacetin, phenylephrine, phenpropanolamine, xanthine (E408, E424). Specimens of uraemic patients may show falsely increased theophylline concentrations (by approximately 3-5 mg/1). 

Immunoassay is the standard method for the determination of theophylline. Theophylline, caffeine, and dyphylline have been sunultaneously quantified by HPLC. 

Fig. 11.2. Separation of some xanthine derivatives and urinary metabolites Column uBondapak C18 (300x4 mm ID), mobile phase acetonitrile - 0.1 M disodium hydrogen phosphate and 0.1 M sodium dihydrogen phosphate in water (2 38), flow rate 1.5 ml/min, detection UV 254 nm. Peaks 1, uric acid 2, creatinine 3, 1-methyluric acid, 3-methyluric acid and 7-methyluric acid 4, xanthine 5, 7-methylxanthine 6, 1,3-dimethyluric acid 7, 3-methyl-xanthine 8, 1-methylxanthine 9, theobromine 10, 8-chlorotheophyl1ine 11, theophylline and 1,7-dimethylxanthine (paraxanthine) 12, dyphylline 13, caffeine, (reproduced with permission from ref. 80, by courtesy of Clinical Chemistry)...

The methylxanthines consist of aminophylline, dyphylline, enprofylline, and pentoxifylline. Aminophylline is the most widely used of the soluble theophyllines. 

Dyphylline is a xanthine derivative related to theophylline. It relaxes bronchial smooth muscle and stimulates central respiratory drive. It is indicated in the relief of acute bronchial asthma and reversible bronchospasm associated with chronic bronchitis and emphysema. A large number of derivatives of the methylxanthines have been prepared and examined for their ability to inhibit cyclic nucleotide phosphodiesterases (PDFs) and antagonize receptor-mediated actions of adenosine, the two best characterized cellular actions of the methylxanthines. Although certain modifications dissociate these two activities to some degree, these compounds are not used therapeutically. 

Dyphylline [l,3-dimethyl-7-(2, 3-dihydroxypropyl)xan-thine] and theophylline inhibit cyclic nucletide PDFs, thereby preventing breakdown of cyclic AMP and cyclic GMP to 5 -AMP and 5 -GMP, respectively. Inhibition of PDFs will lead to an accumulation of cAMP and cGMP, thereby increasing signal transduction through these pathways. The cyclic nucleotide PDFs are members of a superfamily of genetically distinct enzymes. Theophylline and related methylxanthines are relatively nonselective in the PDF subtypes they inhibit. 

Methylxanthines have a few valid therapeutic uses, including treatment of asthma and relief of dyspnea (see Antiasthmatic agents). The CNS stimulatory effects are also utilized for the treatment of the prolonged apnea that may be observed in premature infants. Theophylline may be combined with doxapram (13) for this use (20). The methylxanthine most widely used therapeutically is theophylline, although caffeine may also be used. For parenteral administration, a salt of theophylline is employed. There are several salts available, including theophylline ethylenediamine (aminophylline [317-34-0]) and oxtriphylline (choline theophyllinate). Other synthetic xanthines that are used include dyphylline [479-18-5] and enprofylline [410784)2-8] (21). Caffeine is obtained in pure form from tea waste, from the manufacture of caffeine coffee, and by total synthesis (22,23). 

Simultaneous dyphylline, theophylline, caffeine, aspirin, salicylic acid, procainamide, N-acetylprocainamide... 

Simultaneous acetaminophen, acetylprocainamide, caffeine, dyphylline, procainamide, theophylline... 

Valia, K.H. Hartman, C.A. Kucharczyk, N. Sofia, R.D. Simultaneous determination of dyphylline and theophylline in human plasma by high-performance liquid chromatography. J.Chromatogr., 1980, 221, 170-175... 

Kester, M.B. Saccar, C.L. Mansmann, H.C., Jr. Microassay for the simultaneous determination of theophylline and dyphylline in serum by high-performance liquid chromatography. J.Chromatogr, 1987, 416, 91-97... 

Dyphylline (e.g., Dilor) If n Less potent than theophylline. Less palpitations, nervousness and dizziness than theophylline. 

Dyphylline is the N-7 dihydroxypropyl derivative of theophyiiine and is not a theophylline salt. Dyphylline does not get metabolized to theophylline in vivo, and even though it contains 70% theophylline by molecular weight ratio, the equivalent amount to theophylline is not known. Dosing must be accomplished independently by monitoring dyphylline blood levels. Dyphylline has a diminished bronchodilator effect compared to theophylline, but it may have lower and less serious side effects. Dosage forms available are an elixir and tablets. 

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