from Wikipedia, the free encyclopedia
Structural formula
Structure of theophylline
Surname Theophylline
other names
  • 1,3-dimethyl-3,7-dihydro-1 H -purine-2,6-dione
  • 1,3-dimethylxanthine
Molecular formula C 7 H 8 N 4 O 2
External identifiers / databases
CAS number 58-55-9
EC number 200-385-7
ECHA InfoCard 100,000,350
PubChem 2153
DrugBank DB00277
Wikidata Q407308
Drug information
ATC code
Drug class
Molar mass 180.16 g · mol -1
Melting point
pK s value


  • Slightly soluble in water, ethanol , diethyl ether
  • very soluble in dilute acids or basic solutions
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
06 - Toxic or very toxic


H and P phrases H: 301
P: 301 + 310 + 330
Toxicological data

225 mg kg −1 ( LD 50ratoral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Theophylline (from Latin thea 'tea' and ancient Greek φύλλον phýllon , German 'leaf' ) is a natural substance derived from xanthine from the group of purine alkaloids . The name is derived from tea leaves from which Albrecht Kossel was the first to isolate small amounts of this substance in 1888. Theophylline is also found in small amounts in coffee beans , cola nuts and guarana and is a breakdown product of caffeine in the human metabolism . Theophylline is used therapeutically as a drug against bronchial asthma and other bronchial diseases. Theophylline also increases the performance of the heart and has a diuretic effect.


Albrecht Kossel , discoverer of theophylline

As early as the middle of the 19th century, the London doctor Henry Salter pointed out that the consumption of coffee leads to improvement in asthma attacks. Albrecht Kossel succeeded in isolating theophylline for the first time in 1888 and he gave the substance its current name. Just seven years after its discovery, Emil Fischer and Lorenz Ach succeeded in producing it synthetically, starting from 1,3-dimethyluric acid. Theophylline was thus the first purine alkaloid that could be produced artificially. In 1900 Wilhelm Traube described a chemical synthesis route with the grape synthesis, which is still used today.

After the discovery of the pure substance and its first description as aminophylline designated Ethylendiaminsalzes it was initially as a diuretic ( diuretic used). In 1912, Jakob Pál and Paul Trendelenburg independently demonstrated that xanthines such as caffeine and theophylline have a slackening effect on smooth muscles . In 1921, Hans Guggenheimer introduced theophylline into the treatment of angina pectoris . In 1922 SR Hirsch established methylxanthines such as theophylline in asthma therapy. In 1957, employees at Hoechst discovered the antagonistic effect on adenosine receptors as an important element of its mechanism of action . The development of theophylline preparations with delayed release of active ingredients made it possible in the 1970s to provide satisfactory long-term treatment for asthmatics. With the introduction of glucocorticoids and beta-sympathomimetics for inhalation , theophylline lost its importance again a little later.


Tea bush

Theophylline is an alkaloid that occurs naturally together with other purine alkaloids such as caffeine and theobromine . Compared to the main alkaloids caffeine and theobromine, which can reach a content of up to 6% in plant parts rich in purine alkaloid, the content of the secondary alkaloid theophylline is very low. The highest theophylline content can be found in guarana (up to 0.25%), plant parts of theobroma species (e.g. cocoa, 0.05%), mate leaves (0.05%) and tea leaves (0.03%) become. Theophylline is also found in traces in coffee beans and cola nuts. However, these natural sources are of no economic importance for the extraction of theophylline as a pure substance.


In plants, theophylline may have two different biosynthetic pathways, starting from inosine monophosphate (IMP) and Xanthosinmonophosphat (XMP), which is also key positions in the biosynthesis of cellular energy source adenosine triphosphate (ATP) and guanosine triphosphate take (GTP), and subsequent dephosphorylation to xanthosine are formed. A direct N -3- and N -1-methylation of xanthine leading to theophylline has been postulated. Alternatively, it has been described that the theophylline contained in coffee, tea, cola nuts and guarana is a breakdown product of caffeine.

Theophylline biosynthetic pathways

Even in the human body theophylline may result in a small percentage of reduction of caffeine in the liver by the cytochrome P450 - isoenzyme CYP1A2 are formed.

Clinical information

Application areas (indications)

Theophylline is used in the acute treatment of respiratory distress due to a narrowing of the airways in bronchial asthma and other obstructive airway diseases. Theophylline is also used in the acute treatment of therapy-resistant status asthmaticus and severe acute bronchospasm. Theophylline is available as an infusion for this purpose . In dosage forms for oral use sustained-release ( prolonged-release tablets or capsules) Theophylline is approved for long-term treatment and prevention of asthmatic attacks and other obstructive airway diseases. In the treatment of asthma, it is used both as a long-term therapy and in emergency treatment due to its limited therapeutic range as a reserve in severe cases. An observation of the serum active level, also known as drug monitoring , to ensure the therapeutic success and to avoid undesirable drug effects due to the narrow therapeutic range, is also urgently recommended on the basis of pharmacoepidemiological studies representative of the population .

In paediatrics , theophylline can be used to treat idiopathic respiratory arrest in premature infants and newborns, accompanied by other suitable therapeutic measures for respiratory stimulation. Theophylline is also approved for secondary prophylaxis of apparently life-threatening events in infants (ALTE), although there are insufficient data on a reduction in mortality.

The use of theophylline - outside of its approval - to prevent kidney damage caused by contrast media is controversial. Its use as a diuretic and its previous use in the treatment of angina pectoris are considered obsolete.

Application in veterinary medicine

In veterinary medicine, theophylline is mainly used for bronchial asthma; however, no veterinary medicinal product is currently approved in Germany.

The EU maximum residue limit regulation for food of animal origin allows theophylline to be used in all animal species used for food production.

Contraindications (contraindications)

Theophylline must not be used in cases of known hypersensitivity to this active ingredient, after a recent heart attack or in acute tachycardiac arrhythmias . Theophylline may only be used with great caution and strict indications in patients with unstable angina pectoris , a tendency to tachycardiac arrhythmias, severe high blood pressure , hypertrophic obstructive cardiomyopathy , hyperthyroidism , epilepsy , gastric or duodenal ulcer or the metabolic disease porphyria . Liver and kidney dysfunctions are not a contraindication, but like the use in elderly, multimorbid , seriously ill or intensively treated patients, the dosage must be adjusted and controlled with the aid of drug monitoring.

Use during pregnancy and breastfeeding

Theophylline should be avoided during the first trimester of pregnancy , as there are insufficient data on the use of the active ingredient in this phase of pregnancy. During the second and third trimesters, theophylline can be used after carefully weighing the risks and benefits. In particular are placenta marketability of theophylline and its sympathomimetic take into account properties on the child. If used shortly before the end of pregnancy, sympathomimetic effects on the mother can lead to an inhibition of labor .

Theophylline passes into breast milk and can reach therapeutically effective serum levels in the breastfed infant. Therefore, a risk-benefit analysis should also be carried out, the dosage chosen for the mother as low as possible or, if necessary, weaning .

Drug interactions

Medicinal substances and other exogenous substances ( xenobiotics ) which lead to a decrease or increase in the theophylline concentration in the organism can easily lead either to ineffectiveness of the administered theophylline or to toxic reactions due to the narrow therapeutic range . Enzyme inducers such as barbiturates , carbamazepine , phenytoin , primidone , rifampicin and sulfinpyrazone , but also smoking, lead to an accelerated breakdown of theophylline. The associated decreased plasma levels can be adjusted by a monitored dose increase.

In contrast, inhibitors of the cytochrome P450 enzyme system, in particular CYP-1A2 inhibitors, lead to a reduced breakdown of theophylline, which can lead to an accumulation . Significant interactions in this context could be observed with macrolides (e.g. erythromycin , clarithromycin ), fluoroquinolones (e.g. ciprofloxacin , enoxacin ), thiabendazole , cimetidine and allopurinol . Also, birth control pills , imipenem , isoniazid , calcium antagonists (eg. As verapamil , diltiazem ), propranolol , mexiletine , propafenone , ticlopidine , alpha interferon and influenza vaccines may lead to an increase in the plasma concentration of theophylline and require a controlled dose reduction. An interaction with ranitidine is also possible, but not confirmed.

Theophylline is able to enhance the effects of other xanthines, including caffeine , through a synergism . The effect of β 2 sympathomimetics and diuretics is also increased. The effect of beta blockers and lithium , on the other hand, can be weakened by taking theophylline at the same time. When used simultaneously with halothane , an increase in the cardiac side effects of the inhalation anesthetic was observed.

Side effects

With a frequency of over 10 percent, adverse drug effects on the nervous system, such as headache , tremor , restlessness, excitement and insomnia as well as the metabolism and electrolyte balance such as potassium deficiency ( hypokalaemia ), excess sugar ( hyperglycaemia ), increase in uric acid level ( hyperuricaemia ), increase in serum - calcium ( hypercalcaemia ) and serum creatinine occur. The side effects in the urinary system, which are also very common, are expressed in increased diuresis . This side effect was previously exploited with theophylline as a diuretic. Occasionally (0.1–1%) hypersensitivity reactions to the active substance occur which require a change of the therapeutic agent. The frequency of seizures when theophylline is used as directed has not been quantified .


Side effects depending on the serum level
Serum levels side effect Frequency of
side effects
8-20 µg / ml Tremors, difficulty sleeping,
nausea, heartburn
20-25 µg / ml Restlessness, excitability,
increase in heart rate
> 35 µg / ml Arrhythmias,
low potassium levels ,

Depending on the dose, there are various characteristic side effects listed in the table below. Due to the low therapeutic index of theophylline, an overdose can quickly lead to toxic reactions and even death. The safety of the therapy can be increased by determining the theophylline level from serum or saliva (therapeutic drug monitoring). While in the therapeutic range of 8 to 20 ug / ml iS tremor, insomnia, nausea and restlessness may be observed occur at serum concentrations of about 25 ug / ml seizures, sudden fall in blood pressure, heart rhythm disorders, rhabdomyolysis and serious gastrointestinal disorders in the fore . To avoid serious side effects such as increased heart rate, shortness of breath and seizures, theophylline should be administered intravenously only very slowly and not as a bolus. Particularly severe theophylline intoxication can be fatal.

In the event of slight symptoms of intoxication, the active substance should be discontinued and its serum level determined. Based on these data, therapy can be continued with an adjusted (reduced) dose. If central nervous symptoms such as restlessness and cramps occur, these can be treated with diazepam or phenobarbital . Theophylline antagonizes the effects of benzodiazepines , which are used against seizures of various causes. As a result, seizures caused by theophylline may result in a higher need for benzodiazepines. In a retrospective study of theophylline-induced seizures in children, around a quarter of the patients also had to be intubated . If threatening cardiac arrhythmias occur, intravenous administration of beta blockers is indicated for non-asthmatics or verapamil for asthmatics. When vital functions are threatened, vital functions are monitored, the airways are kept clear and the supply of oxygen, theophylline residues are removed from the gastrointestinal tract by gastric lavage and activated charcoal , the water and electrolyte balance is monitored and, if necessary, volume replacement is also included Plasma expanders in the foreground. With the help of hemodialysis and hemoperfusion , rapid and complete detoxification can also be achieved in the case of particularly severe intoxications.

Pharmacological properties

Mode of action (pharmacodynamics)

Theophylline primarily leads to a relaxation of the smooth muscles of the airways and thus to an expansion of the bronchi. In addition, this medicinal substance increases the removal of foreign substances and mucus through the cilia of the lungs, lowers the pressure in the pulmonary vessels and increases the respiratory drive and the ability of the respiratory muscles to contract. Theophylline's anti-inflammatory effects can also contribute to its asthma effectiveness with long-term treatment.

At the molecular level, various mechanisms are held responsible for theophylline's anti-asthmatic effectiveness. As a non-selective inhibitor ( inhibitor ) of the phosphodiesterases theophylline leads to an increase of this in the cell cAMP . Additionally, theophylline acts antagonistically to A 1 - and A 2 - adenosine receptors . In this way, on the one hand, the release of inflammatory mediators , such as histamine and leukotrienes , is inhibited and, on the other hand, the concentration of cellular cAMPs is further increased. The relaxation of the smooth muscles, but possibly also secondary effects, such as the release of interleukin-10 , the inhibition of the inflammatory transcription factor NF-κB and effects on the controlled cell death ( apoptosis ) of granulocytes and T lymphocytes can be attributed to the increase in cAMP become. At very high theophylline concentrations , which are of no therapeutic relevance, theophylline leads to an inhibition of calcium channels .

The anti-inflammatory active component of theophylline is also associated with an increase in the activity of histone deacetylases in genes that code for inflammation mediators .


After infusion of theophylline, the bronchodilator effect sets in within a few minutes as soon as a plasma level of 5 µg / ml is reached. The bronchodilator effect lasts for about six to eight hours. After oral administration of a theophylline solution, the active ingredient is absorbed quickly and completely. The bronchodilator effect also occurs within a few minutes. For long-term treatment, sustained-release preparations are used, which reach their maximum effect after around six to eight hours.

In the therapeutic concentration range, theophylline is 60% bound to plasma proteins. The plasma protein binding in newborns and in patients with cirrhosis of the liver is reduced and is around 40%.

Theophylline is almost completely broken down by the cytochrome P450 enzyme system in the liver. The rate of metabolism, however, varies greatly from person to person and depends, among other things, on the living situation (especially age, physical strain and body weight), the eating habits and smoking habits of the patient. Decreased degradation rates can be observed in patients with febrile infections, liver damage and right heart failure . The plasma half-life is usually between 7 and 9 hours in healthy adults. For smokers this is significantly reduced to 4 to 5 hours and for children to 3 to 4 hours. The plasma half-life is 6 hours in dogs, 8 hours in cats, 11 hours in pigs and 10 to 17 hours in horses.

In particular, drugs that inhibit or induce degradation via the cytochrome system have a significant influence on the plasma half-life of theophylline . The cytochrome P450 inhibitors cimetidine , allopurinol , oral contraceptives , macrolides and fluoroquinolones, for example, lead to a slower breakdown and thus to an accumulation of theophylline. Enzyme inducers such as phenytoin , carbamazepine , rifampicin , isoniazid and barbiturates , but also smoking tobacco or marijuana , on the other hand, lower theophylline levels. The consumption of caffeine can also lead to a reduced breakdown of theophylline. A genetic polymorphism of the CYP1A2 gene has been described, which leads to a reduced breakdown of theophylline.



Equilibrium between the 7 H and 9 H tautomers of theophylline

Theophylline is a white, odorless, amorphous or crystalline powder with a bitter taste. It can come in two polymorphic forms and as a monohydrate. Form II is the form that is stable at room temperature. It melts at 271 ° C with a heat of fusion of 167.1 J · g −1 . Form I has a melting point of 275 ° C with a heat of fusion of 155.5 J · g −1 . Both forms are enantiotropic to one another. As a salt ( monohydrate , lysine salt or magnesium acetate ) it is stable in the air, the free base decomposes when exposed to air and light. The alkaloid is amphoteric and can be used as a weak acid with an acid constant pK s 2 of 8.6 (deprotonation of the imidazole nitrogen in position 7) or as a weak base with a pK s 1 value of 0.3 (protonation equilibrium of the imidazole nitrogen in position 9) react. In aqueous solution, theophylline, like purine , is in a tautomeric equilibrium, with the 9 H tautomer predominating. Due to its amphoteric nature, theophylline dissolves well in dilute acids or basic solutions. In contrast, the substance is sparingly soluble in water, ethanol or diethyl ether . With the aim of improving the solubility, theophylline salts such as theophylline diethanolamine, theophylline ethanolamine, theophylline isopropanolamine, theophylline sodium acetate and theophylline sodium glycinate have been developed. In addition to the anhydrous theophylline, its monohydrate as well as theophylline sodium glycinate and theophylline ethylenediamine ( aminophylline ) are used pharmaceutically .


Theophylline is a derivative of xanthine. It can be produced by reacting the starting materials N , N '-dimethylurea and ethyl cyanoacetate with the help of the grape synthesis . The synthesis route was published as early as 1900 in the journal Chemical Reports by Wilhelm Traube from the Chemical Department of the Pharmacological Institute in Berlin .

Synthesis of theophylline


Because of its pharmacological properties, theophylline has been a popular object for structural modifications in medicinal chemistry . In particular, changes in the substituents in the 7 and 8 positions led to new drugs. The derivatives that have achieved therapeutic relevance include 8-chlorotheophylline , fenetylline , etofylline , cafedrine and reproterol .


The classic murexide reaction can be used to identify theophylline, which results in a positive reaction for theophylline, as well as for other methylxanthines. In addition, the theophyllidine reaction , which is based on an alkaline hydrolysis of theophylline and a coupling with diazotized sulfanilic acid , can be used to detect theophylline. A positive proof can also be achieved with the help of Gibbs reagent . The Zwikker reaction is suitable for distinguishing between theophylline and other methylxanthines . In addition, in contrast to caffeine and theobromine, theophylline forms a white precipitate with silver nitrate in an ammoniacal environment .

The theophylline content is determined according to the European Pharmacopoeia as titration with the help of alkalimetry . Since the content of theophylline cannot be determined directly in the aqueous medium due to the comparatively low acid strength, titration with sodium hydroxide solution is carried out after precipitation and deprotonation with silver nitrate using the indicator bromothymol blue . Alternative methods of determining levels include instrumental methods such as HPLC .

The determination of theophylline in biological samples is determined by their nature. For relatively simple analysis samples , methods such as thin-layer chromatography , also in combination with UV or IR spectroscopy , are used. More complex samples, such as B. blood , serum and urine , however, require more complex methods for qualitative and quantitative determination such. B. Enzyme immunoassays , gas chromatography with mass spectrometry coupling (GC / MS) or liquid chromatography with mass spectrometry coupling (HPLC / MS).

Trade names

Theophylline is available as a single preparation under the trade names Aerobin (D), Afonilum (D), Bronchoretard (D), Euphyllin retard (A, CH), Euphylong (D), Respicur retard (A), Solosin retard (D), Theolair (CH), Theospirex retard (A), Tromphylline (D), Unifyl (A, CH) and Uniphyllin (D) as well as generic names in the form of tablets or capsules with a delayed release (retardation) in single doses between 100 and 600 mg expelled. Solosin drops (D) and Euphylong quick (D) are offered as non-delayed preparations for acute cases . Are also available for the acute case afpred forte-THEO (D), Bronchoparat (D), Euphyllin (A, CH), Euphylong iv (D), RESPICUR ampoules (A), Solosin infusion solution (D) and Theospirex ampoules (A) to Infusion available. As a combination product with ambroxol is Broncho Euphyllin (D) in the trade.

Web links

Commons : Theophylline  - Collection of images, videos and audio files
Wiktionary: Theophylline  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. a b c d e P. Szerner, B. Legendre, M. Sghaier: Thermodynamic properties of polymorphic forms of theophylline. Part I: DSC, TG, X-ray study . In: J. Therm. Anal. Calorim. tape 99 , 2010, p. 325-335 , doi : 10.1007 / s10973-009-0186-1 (English).
  2. ^ A b c d e f F. von Bruchhausen, Hermann Hager: Hager's manual of pharmaceutical practice. Volume 9: Fabrics P-Z. 5th edition. Birkhäuser, 1999, ISBN 3-540-52688-9 , pp. 853-855.
  3. Entry on theophylline. In: Römpp Online . Georg Thieme Verlag, accessed on March 10, 2011.
  4. a b Entry on theophylline in the GESTIS substance database of the IFA , accessed on January 8, 2018(JavaScript required) .
  5. Theophylline data sheet from Sigma-Aldrich , accessed on April 24, 2011 ( PDF ).
  6. ^ H. Salter: On some points in the treatment and clinical history of asthma . In: Edinb. Med. J. Band 4 , 1859, p. 1109-1115 (English).
  7. A. Kossel: About a new base from the plant kingdom. In: Ber. German Chem. Ges. Volume 21 , 1888, p. 2164-2167 , doi : 10.1002 / cber.188802101422 .
  8. A. Kossel: About the theophylline, a new component of thees. In: Hoppe Seylers Z Physiol Chem . tape 13 , 1889, p. 298-308 .
  9. E. Fischer, L. Ach: Synthesis of Caffeine. In: Ber. German Chem. Ges. Volume 28 , 1895, p. 3135-3143, here 3139 , doi : 10.1002 / cber.189502803156 .
  10. a b Wilhelm Traube: About a new synthesis of guanine and xanthine . In: Chem. Ber. tape 33 , no. 1 , 1900, p. 1371-1383 , doi : 10.1002 / cber.190003301236 .
  11. a b Wilhelm Traube: The synthetic structure of uric acid, xanthine, theobromine, theophylline and caffeïns from cyanoacetic acid . In: Chem. Ber. tape 33 , no. 3 , October 1900, p. 3035-3056 , doi : 10.1002 / cber.19000330352 .
  12. O. Minkowski: About Theocin (theophylline) as a diuretic. In: Ther. Present . tape 43 , 1902, pp. 490-493 .
  13. H. Guggenheimer: Euphylline intravenously as a cardiac agent . In: Ther. Monthly books . tape 35 , 1921, pp. 566-572 .
  14. G. Schultze-Werninghaus, J. Meier-Sydow: The clinical and pharmacological history of theophylline: first report on the bronchospasmolytic action in man by SR Hirsch in Frankfurt (Main) 1922. In: Clin. Allergy . tape 12 , 1982, pp. 211-215 , PMID 7042115 (English).
  15. Klaus Aktorius (Ed.): General and special pharmacology and toxicology. 10th edition. Munich 2009, ISBN 978-3-437-42522-6 , pp. 188-189.
  16. BB Fredholm, CG Persson: Xanthine derivatives as adenosine receptor antagonists . In: European Journal of Pharmacology . tape 81 , no. 4 , 1982, pp. 673-676 , PMID 6288418 (English).
  17. ^ MA Jalal, HA Collin: Estimation of caffeine, theophylline and theobromine in plant material . In: New Phytol. tape 76 , 1976, pp. 277–281 , doi : 10.1111 / j.1469-8137.1976.tb01461.x (English).
  18. Rudolf Hänsel, Otto Sticher: Pharmakognosie, Phytopharmazie. 8th edition. Springer-Verlag, 2007, ISBN 978-3-540-26508-5 , p. 1455.
  19. James A. Duke: Handbook of phytochemical constituents of GRAS herbs and other economic plants. CRC Press, Boca Raton FL 1992, ISBN 0-8493-3672-4 .
  20. T. Suzuki, E. Takahashi: Biosynthesis of caffeine by tea-leaf extracts. Enzymic formation of theobromine from 7-methylxanthine and of caffeine from theobromine. In: Biochem. J. 146, 1975, pp. 87-96. PMID 238504 .
  21. Kyoto Encyclopedia of Genes, Genomes: Biosynthesis of alkaloids derived from histidine and purine .
  22. T. Suzuki, GR Waller: Biosynthesis and biodegradation of caffeine, theobromine, and theophylline in Coffea arabica L. fruits. In: J. Agric. Food Chem. 32 (4), 1984, pp. 845-848. doi: 10.1021 / jf00124a038 .
  23. a b BfArM sample text for technical information 8000368: Theophylline concentrate for the preparation of an infusion solution (as of June 17, 2008; RTF ; 117 kB).
  24. a b c d B. Lemmer , R. Wettengel: Diseases of the respiratory tract. In: Björn Lemmer, Kay Brune: Pharmacotherapy - Clinical Pharmacology. 13th edition. Heidelberg 2007, ISBN 978-3-540-34180-2 , pp. 343-344, pp. 349-350.
  25. a b c d e f g h i j BfArM sample text for specialist information 8000370: Theophylline - retard tablet, retard capsule, retard granulate (as of June 17, 2008; RTF; 120 kB).
  26. a b Gerd Herold: Internal Medicine. Cologne 2009, ISBN 978-1-111-15195-9 , pp. 343–346.
  27. D. Ukena, LT Fishman, WB Niebling: Bronchial asthma - diagnosis and therapy in adulthood. In: Deutsches Ärzteblatt . 105 (21), 2008, pp. 385-394.
  28. U. Langen, H. Knopf, HU Melchert: Medicinal therapy of bronchial asthma. Results of the Federal Health Survey 1998. In: Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz . 49 (9), Sep 2006, pp. 903-910. PMID 16927032 .
  29. SM Bagshaw, WA Ghali: Theophylline for prevention of contrast-induced nephropathy: a systematic review and meta-analysis. In: Arch Intern Med . 165, 2005, pp. 1087-1093. PMID 15911721 .
  30. a b Wolfgang Löscher: Theophylline. In: Wolfgang Löscher et al. (Ed.): Pharmacotherapy for pets and farm animals. 7th edition. Paul Parey Verlag, 2006, ISBN 3-8304-4160-6 , p. 115.
  31. S. Rau: The History of Diuretics: From Caffeine to Furosemide . In: Pharmacy in our time . tape 35 , no. 4 , 2006, p. 286-292 , PMID 16886504 .
  32. Heinz Lüllmann, Klaus Mohr, Lutz Hein: Pharmacology and Toxicology. 16th edition. Stuttgart 2006, ISBN 3-13-368516-3 , p. 176.
  33. ^ H. Yoshikawa: First-line therapy for theophylline-associated seizures. In: Acta Neurol Scand. 115 (4), Apr 2007, pp. 57-61. PMID 17362277 .
  34. ^ PJ Barnes: Theophylline: new perspectives for an old drug. In: Am J Respir Crit Care Med . 167, 2003, pp. 813-818. PMID 12623857 .
  35. K. Ito, S. Lim, G. Caramori, B. Cosio, KF Chung, IM Adcock, PJ Barnes: A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. In: Proc Natl Acad Sci USA . 99 (13), Jun 25, 2002, pp. 8921-8926. PMID 12070353 .
  36. ^ JH Jonkman, RA Upton: Pharmacokinetic drug interactions with theophylline . In: Clinical Pharmacokinetics . tape 9 , no. 4 (Jul – Aug), August 1984, pp. 309-334 , PMID 6147220 .
  37. ^ P. Kozak: Factors that influence theophylline metabolism. In: Western Journal of Medicine . tape 131 , no. 4 , October 1979, p. 319-320 , PMC 1271836 (free full text).
  38. Yasushi Obase, Terufumi Shimoda, Tetsuya Kawano, Sachiko Saeki, Shin-ya Tomari, Kazuko Mitsuta-Izaki, Hiroto Matsuse, Moritoshi Kinoshita, Shigeru Kohno: Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma . In: Clin Pharmacol Ther . tape 73 , no. 5 , 2003, p. 468-474 , PMID 12732846 .
  39. Theophylline . In: Commentary on the Ph. Eur.
  40. European Pharmacopoeia 6.0. Volume 3: Monograph Theophylline. Deutscher Apotheker Verlag, Stuttgart 2008, ISBN 978-3-7692-3962-1 , pp. 4116-4117.
  41. H. Juárez-Olguín, J. Flores-Pérez, I. Lares-Asseff: Plasmatic levels of theophylline in asthmatic patients. Comparative evaluations of two different methods. In: Arch Med Res . 29 (1), 1998, pp. 45-50. PMID 9556922 .
  42. M. Kress, D. Meissner, P. Kaiser, R. Hanke, WG Wood: Determination of theophylline by HPLC and GC-IDMS, the effect of chemically similar xanthine derivatives on the specificity of the method and the possibility of paracetamol as interfering substance. In: Clin Lab. 48 (9-10), 2002, pp. 541-551. PMID 12389716 .
  43. Red List online, as of October 2009.
  44. AM comp. d. Switzerland, as of October 2009.
  45. AGES-PharmMed, as of October 2009.
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