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Licensed Unlicensed Requires Authentication Published by De Gruyter April 18, 2015

Comparative study of the efficacy and safety of theophylline and doxofylline in patients with bronchial asthma and chronic obstructive pulmonary disease

  • Dushyant Lal EMAIL logo , Sachin Manocha , Arunabha Ray , V.K. Vijayan and Raj Kumar


Background: Bronchial asthma and chronic obstructive pulmonary disease (COPD) are the major obstructive disorders that may contribute to the severity in individual patients. The present study was designed to compare the efficacy and safety of theophylline and doxofylline in patients with bronchial asthma and COPD.

Methods: A total of 60 patients, 30 each with bronchial asthma and COPD, were enrolled for the study. Each group of 30 patients received standard treatment for asthma and COPD. Each group was again subdivided into two with 15 patients each, who received theophylline or doxofylline in addition to standard therapy, for a period of 2 months. Each patient was followed up fortnightly for the assessment of efficacy parameters using a pulmonary function test (PFT), clinical symptoms and emergency drug use, and safety was assessed by recording adverse drug reactions.

Results: Both theophylline and doxofylline produced enhancements in PFT at different time intervals in both asthma and COPD patients. The maximum beneficial effects were seen at 6 weeks for asthma patients and at 8 weeks for COPD patients for both theophylline and doxofylline.

Conclusions: The comparative study showed that doxofylline was more effective as evidenced by improvement in PFT as well as clinical symptoms, and reduced incidence of adverse effects and emergency bronchodilator use.

Corresponding author: Dr. Dushyant Lal, Assistant Professor, Department of Pharmacology, ESIC Dental College and Hospital, Rohini, New Delhi 110089, India, E-mail:


1. Salgado Garcia C, Jimenez Heffernan A, Sanchez de Mora E, Ramos Font C, Lopez Martin J, Rivera de los Santos F, et al. Comparative study of the safety of regadenoson between patients with mild/moderate chronic obstructive pulmonary disease and asthma. Eur J Nucl Med Mol Imaging 2014;41: 119–25.10.1007/s00259-013-2493-9Search in Google Scholar

2. Reddy KS, Gupta PC. Report on tobacco control in India. New Delhi: Ministry of Health and Family Welfare, Government of India, 2004:99–102.Search in Google Scholar

3. Vijayan VK. Chronic obstructive pulmonary disease. Indian J Med Res 2013;137:251–69.Search in Google Scholar

4. Lommatzsch M, Virchow CJ. Severe asthma: definition, diagnosis and treatment. Dtsch Arztebl Int 2014;111:847–55.Search in Google Scholar

5. National Heart Lung and Blood Institute: Global initiative for asthma: NHLBI/WHO workshop report. Global strategy for asthma management and prevention, 2008.Search in Google Scholar

6. Albertson TE, Sutter ME, Chan AL. The acute management of asthma. Clin Rev Allergy Immunol 2015;48:114–25.10.1007/s12016-014-8448-5Search in Google Scholar

7. Cazzola M, Matera MG. Bronchodilators: current and future. Clin Chest Med 2014;35:191–201.10.1016/j.ccm.2013.10.005Search in Google Scholar

8. Barnes PJ. Theophylline. Am J Respir Crit Care Med 2013;188:901–6.10.1164/rccm.201302-0388PPSearch in Google Scholar

9. Culpitt SV, De Matos C, Russell RE, Donnelly LE, Rogers DF, Barnes PJ. Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in COPD. Am J Resp Crit Care Med 2002;165:1371–6.10.1164/rccm.2105106Search in Google Scholar

10. Barnes PJ. Theophylline: new perspectives for an old drug. Am J Respir Crit Care Med 2003;167:813–8.10.1164/rccm.200210-1142PPSearch in Google Scholar

11. Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, et al. A molecular mechanism of action of theophylline: induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci USA 2002;99:8921–6.10.1073/pnas.132556899Search in Google Scholar

12. Ito K, Ito M, Elliott WM, Cosio B, Caramori G, Kon OM, et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med 2005;352:1967–76.10.1056/NEJMoa041892Search in Google Scholar

13. Tohda Y, Muraki M, Iwanaga T, Kubo H, Fukuoka M, Nakajima S. The effect of theophylline on blood and sputum eosinophils and ECP in patients with bronchial asthma. Int J Immunopharmacol 1998;20:173–81.10.1016/S0192-0561(98)00026-5Search in Google Scholar

14. Coward WR, Sagara H, Church MK. Asthma, adenosine, mast cells and theophylline. Clin Exp Allergy 1998;28:42–6.Search in Google Scholar

15. Gerard JM, Delecluse F, Robience Y. Theophylline-induced shuttering. Mov Disord 1998;13:847–8.10.1002/mds.870130518Search in Google Scholar PubMed

16. Krieger AC, Takeyasu M. Nonconvulsive status epilepticus in theophylline toxicity. J Toxicol Clin Toxicol 1999;37:99–101.10.1081/CLT-100102414Search in Google Scholar

17. Bucca C, Rolla G, Fonzo D, Franzone JS, Di Carlo R. Acute clinical-pharmacological findings in obstructive pneumopathy following 2(7,-theophyllinmethyl) 1,3-dioxolane (doxofylline). Int J Clin Pharm Res 1982;4:101–3.Search in Google Scholar

18. Poggi R, Brandolese R, Bernasconi M, Manzin E, Rossi A. Doxofylline and respiratory mechanics. Short-term effects in mechanically ventilated patients with airflow obstruction and respiratory failure. Chest 1989;96:772–8.10.1378/chest.96.4.772Search in Google Scholar

19. Dini FL, Roberto C. Doxofylline – a new generation xanthine bronchodilator devoid of major cardiovascular side effects. Curr Med Res Opin 2001;16:258–68.10.1185/030079901750120196Search in Google Scholar

20. Barnes PJ, Pauwels RA. Theophylline in the management of asthma: time for reappraisal? Eur Respir J 1994;7:579–91.10.1183/09031936.94.07030579Search in Google Scholar

21. Cirillo R, Barone D, Franzone JS. Doxofylline, an antiasthmatic drug lacking affinity for adenosine receptors. Arch Int Pharmacodyn 1988;295:221–37.Search in Google Scholar

22. Goldstein MF, Chervinsky P. Efficacy and safety of doxofylline compared to theophylline in chronic reversible asthma: a double-blind randomized placebo-controlled multicentre clinical trial. Med Sci Monit 2002;8:CR297–304.Search in Google Scholar

23. van Mastbergen J, Jolas T, Allegra L, Page CP. The mechanism of action of doxofylline is unrelated to HDAC inhibition, PDE inhibition or adenosine receptor antagonism. Pulm Pharmacol Ther 2012;25:55–61.10.1016/j.pupt.2011.10.007Search in Google Scholar

24. Franzone JS, Cirillo R, Reboani MC. Doxofylline differs from methylxanthines in its movement of cytosolic calcium. Int J Tissue React 1991;18:131–8.Search in Google Scholar

25. Lazzaroni M, Grossi E, Porro GB. The effect of intravenous doxofylline or aminophylline on gastric secretion in duodenal ulcer patients. Aliment Pharmacol Ther 1990;4:643–9.10.1111/j.1365-2036.1990.tb00512.xSearch in Google Scholar

26. Sacco C, Braghiroli A, Grossi E, Donner CF. The effects of doxofylline vs. teophylline on sleep architecture in COPD patients. Monaldi Arch Chest Dis 1995;50:98–103.Search in Google Scholar

27. Kobzik L. The lung. In: Cotran RS, Kumar V, Collins T, editors. Robbins pathological basis of diseases, 7th ed. Philadelphia: W.B. Saunders, 1999:706–7.Search in Google Scholar

28. CDC Office of Communication. The health consequences of smoking: a report of the surgeon general. CDC Office of Communication, 2004. Available at Accessed 13 March 2009.Search in Google Scholar

29. O’Shaughnessy TC, Ansari TW, Barnes NC, Jeffery PK. Inflammation in bronchial biopsies of subjects with chronic bronchitis: inverse relationship of CD8+ T lymphocytes with FEV1. Am J Respir Crit Care Med 1997;155:852–7.10.1164/ajrccm.155.3.9117016Search in Google Scholar

30. Pesci A, Balbi B, Majori M, Cacciani G, Bertacco S, Alciato P, et al. Inflammatory cells and mediators in bronchial lavage of patients with chronic obstructive pulmonary disease. Eur Respir J 1998;12:380–6.10.1183/09031936.98.12020380Search in Google Scholar

31. Dong KZ, Zhu YM. Effect of heche chongcao capsule on expression of TNF-α protein in rats with chronic obstructive pulmonary disease. Zhongguo Zhong Xi Yi Jie He Za Zhi 2014;34:1342–6.Search in Google Scholar

32. MacNee W, Rahman I. Is oxidative stress central to the pathogenesis of chronic obstructive pulmonary disease? Trends Mol Med 2000;7:43–62.10.1016/S1471-4914(01)01912-8Search in Google Scholar

33. Calverley PM, Burge PS, Spencer S, Anderson JA, Jones PW. Bronchodilator reversibility testing in chronic obstructive pulmonary disease. Thorax 2003;58:659–64.10.1136/thorax.58.8.659Search in Google Scholar PubMed PubMed Central

34. National Family Health Survey-2 (NFHS-2), India 1998–99 International Institute of Population Studies, 2000.Search in Google Scholar

35. Killian KJ, Watson R, Otis J, St Amand TA, O’Byrne PM. Symptom perception during acute bronchoconstriction. Am J Respir Crit Care Med 2000;162:490–6.10.1164/ajrccm.162.2.9905079Search in Google Scholar PubMed

36. Franzone JS, Cirillo R, Reboani MC. Pharmacological studies in animals of β-hydroxyethyl-theophylline, the major metabolite of doxofylline in humans. Meth Find Exp Clin Pharmacol 1991;13:289–99.Search in Google Scholar

37. Gulati K, Ray A, Pal G, Vijayan VK. Possible role of free radicals in theophylline induced seizures in mice. Pharmacol Biochem Behav 2005;82:241–5.10.1016/j.pbb.2005.06.019Search in Google Scholar PubMed

38. Tyagi N, Gulati K, Vijayan VK, Ray A. A study to monitor adverse drug reactions in patients of chronic obstructive lung disease: focus on theophylline. Indian J Chest Dis All Sci 2008;50:199–202.Search in Google Scholar

39. Sankar J, Lodha R, Kabra SK. Doxofylline – the next generation methylxanthine. Indian J Pediatr 2008;75:251–4.10.1007/s12098-008-0054-1Search in Google Scholar PubMed

40. Cogo R, Castronuovo A. Effects of oral doxofylline on inflammatory changes and altered cell proliferation in chronic obstructive bronchitis. Eur Rev Med Pharmacol Sci 2000;4:15–20.Search in Google Scholar

41. Conti G, Cogliati AA, Antonelli M, Dell’utri D, Lappa A, De Blasi RA, et al. Doxofylline reduces airways resistances in patients with adult respiratory distress syndrome. Acta Anaesthesiol Ital 1994;45(Suppl):47–53.Search in Google Scholar

42. Houtmeyers E, Gosselink R, Gayan-Ramirez G, Decramer M. Effects of drugs on mucus clearance. Eur Respir J 1999;14:452–67.10.1034/j.1399-3003.1999.14b35.xSearch in Google Scholar PubMed

Received: 2015-1-21
Accepted: 2015-3-9
Published Online: 2015-4-18
Published in Print: 2015-9-1

©2015 by De Gruyter

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