Analysis of Plasma Concentrations of Theophylline in Smoking and Nonsmoking Patients with Asthma

Zlatica Goseva; Angelko Gjorcev; Biserka Jovkovska Kaeva; Elena Jovanovska Janeva; Irina Angelovska

doi:10.3889/oamjms.2015.117

Authors

Zlatica Goseva University Clinic of Pulmonology and Allergology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
Angelko Gjorcev University Clinic of Pulmonology and Allergology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
Biserka Jovkovska Kaeva University Clinic of Pulmonology and Allergology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
Elena Jovanovska Janeva University Clinic of Pulmonology and Allergology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje
Irina Angelovska University Clinic of Pulmonology and Allergology, Faculty of Medicine, Ss Cyril and Methodius University of Skopje, Skopje

DOI:

https://doi.org/10.3889/oamjms.2015.117

Keywords:

asthma, theophylline, plasma concentration, cigarette smoking, theophylline clearance

Abstract

BACKGROUND: While dosing theophylline in asthmatics, we should consider that a lot of medicines, substances, conditions and diseases affect the clearance of theophylline, such as smoking, macrolide antibiotics, barbiturates, oral contraceptives, heart and liver insufficiency, alcohol, calcium-antagonists, pneumonia, viral infections, hypoxemia, etc.

AIM: The aim of the study is to investigate the concentrations of theophylline during the day in smoking and nonsmoking patients with asthma.

MATERIAL AND METHODS: We have estimated the concentrations of theophylline 6 times daily by the HPLC method (Keith Muir, J Chromatography) in 20 smoking and 20 nonsmoking asthmatic patients, who were treated with theophylline sustained-release tablets 175 mg twice daily.

RESULTS: In the first group of 20 nonsmoking patients we obtained constant therapeutic and optimal concentrations of theophylline. In the second group of 20 smoking asthmatics the concentration of theophylline in plasma, in 8pm and 8am the next day was very low.

CONCLUSION: Because in smokers we have increased clearance and the decreased half- life of theophylline, and in order to prevent the night time life-threatening attacks, it is necessary to recommend maximal doses of theophylline, especially in the evening. According to the study, dosage should be individualized in order to optimize the treatment based on the measurement of theophylline concentration in plasma.

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References

Global Initiative for Asthma (GINA), GINA Report 2015, Global Strategy for Asthma Management and Prevention, updated 2015.

Barnes PJ. Theophylline. Am J Respir Crit Care Med. 2013;188(8):901-6.

http://dx.doi.org/10.1164/rccm.201302-0388PP DOI: https://doi.org/10.1164/rccm.201302-0388PP

PMid:23672674

Kawai M, Kato M. Theophylline for the treatment of bronchial asthma: Present status. Methods Find Exp Clin Pharmacol. 2000;22(5):309.

http://dx.doi.org/10.1358/mf.2000.22.5.796650 DOI: https://doi.org/10.1358/mf.2000.22.5.796650

PMid:11031732

Tilley SL. Handbook of Experimental Pharmacology. Methylxanthines in Asthma, 2011:pp 439-456.

http://dx.doi.org/10.1007/978-3-642-13443-2_17 DOI: https://doi.org/10.1007/978-3-642-13443-2_17

MorfÃn Maciel BM, Castillo MorfÃn BM. Theophylline, a new look to an old drug. Rev Alerg Mex. 2010;57(4):112-22.

PMid:21255523

Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, Barnes PJ. A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci USA. 2002;99(13):8921-6.

http://dx.doi.org/10.1073/pnas.132556899 DOI: https://doi.org/10.1073/pnas.132556899

PMid:12070353 PMCid:PMC124399

Zevin S, Benowitz NL. Drug interactions with tobacco smoking. An update. Clin Pharmacokinet. 1999;36(6):425-38.

http://dx.doi.org/10.2165/00003088-199936060-00004 DOI: https://doi.org/10.2165/00003088-199936060-00004

PMid:10427467

Thomson NC, Chaudhuri R, Livingston E. Asthma and cigarette smoking. European Respiratory Journal. 2004;24:822â€“833.

http://dx.doi.org/10.1183/09031936.04.00039004 DOI: https://doi.org/10.1183/09031936.04.00039004

PMid:15516679

Muir KT, Jonkman JH, Tang DS, Kunitani M, Riegelman S. Simultaneous determination of theophylline and its major metabolites in urine by reversed-phase ion-pair high-performance liquid chromatography. Journal of Chromatography B: Biomedical Sciences and Applications. 1980;221(1): 85-95.

http://dx.doi.org/10.1016/S0378-4347(00)81010-5 DOI: https://doi.org/10.1016/S0378-4347(00)81010-5

Thomson NC. Smokers with asthma: what are the management options? Am J Respir Crit Care Med. 2007;175(8):749-50.

http://dx.doi.org/10.1164/rccm.200701-017ED DOI: https://doi.org/10.1164/rccm.200701-017ED

PMid:17484086

Chalmers GW, et al. Smoking and airway inflammation in patients with mild asthma. Chest. 2001;120(6):1917-22.

http://dx.doi.org/10.1378/chest.120.6.1917 DOI: https://doi.org/10.1378/chest.120.6.1917

PMid:11742922

Hylkema NM, Sterk PJ, De Boer WI, Postma DS. Tobacco use in relation to COPD and asthma. Eur Resp J. 2007: 29(3):438-445.

http://dx.doi.org/10.1183/09031936.00124506 DOI: https://doi.org/10.1183/09031936.00124506

PMid:17329490

Kroon LA. Drug interactions with smoking. Am J Health-Syst Pharm. 2007;64:1917-1921.

http://dx.doi.org/10.2146/ajhp060414 DOI: https://doi.org/10.2146/ajhp060414

PMid:17823102

Thomson NC, Spears M. The influence of smoking on the treatment response in patients with asthma. Curr Opin Allergy Clin Immunol. 2005;5(1):57-63.

http://dx.doi.org/10.1097/00130832-200502000-00011 DOI: https://doi.org/10.1097/00130832-200502000-00011

Spears M, et al. Effect of low-dose theophylline plus beclometasone on lung function in smokers with asthma: a pilot study. Eur Resp J. 2009;33(5):1010-1017.

http://dx.doi.org/10.1183/09031936.00158208 DOI: https://doi.org/10.1183/09031936.00158208

PMid:19196814

Stapleton M, Howard-Thompson A, George Ch, Hoover MR, Self HT. Smoking and Asthma. J Am Board Fam Med. 2011;24:313-322.

http://dx.doi.org/10.3122/jabfm.2011.03.100180 DOI: https://doi.org/10.3122/jabfm.2011.03.100180

PMid:21551404

An-Soo Jang, at al. The Impact of Smoking on Clinical and Therapeutic Effects in Asthmatics. J Korean Med Sci. 2009;24(2):209-214.

http://dx.doi.org/10.3346/jkms.2009.24.2.209 DOI: https://doi.org/10.3346/jkms.2009.24.2.209

PMid:19399260 PMCid:PMC2672118