Plasma concentrations of inhaled corticosteroids in relation to airflow obstruction in asthma
Article first published online: 10 JUL 2006
British Journal of Clinical Pharmacology
Volume 62, Issue 4, pages 412–419, October 2006
How to Cite
Mortimer, K. J., Harrison, T. W., Tang, Y., Wu, K., Lewis, S., Sahasranaman, S., Hochhaus, G. and Tattersfield, A. E. (2006), Plasma concentrations of inhaled corticosteroids in relation to airflow obstruction in asthma. British Journal of Clinical Pharmacology, 62: 412–419. doi: 10.1111/j.1365-2125.2006.02712.x
- Issue published online: 10 JUL 2006
- Article first published online: 10 JUL 2006
- Received 4 December 2005Accepted 6 April 2006Published OnlineEarly10 July 2006
- airflow obstruction;
- inhaled corticosteroid;
To compare the pharmacokinetic profiles of beclometasone, budesonide, fluticasone and mometasone following inhalation in patients with asthma, and explore the relationship between lung function and plasma drug concentrations.
Thirty subjects with asthma and a forced expiratory volume in 1 s (FEV1) ranging from 36 to 138% predicted, inhaled 800 µg beclometasone, budesonide and mometasone and 1000 µg fluticasone in random order. Plasma drug concentrations were measured over 8 h and the relationship between the area under the plasma concentration–time curve (AUC0−8) and lung function was modelled using linear regression. Estimated AUC0−8 values at 50 and 100% predicted FEV1 were compared for each drug.
Pharmacokinetic profiles differed markedly between the drugs. Correlation coefficients for the relation between FEV1% predicted and AUC0−8 values for beclometasone, budesonide, fluticasone and mometasone were 0.37 (P = 0.05), 0.33 (P = 0.08), 0.25 (P = 0.2) and 0.52 (P = 0.004), respectively, and estimated AUC0−8 values were 1.3 [95% confidence interval (CI) 1.0, 1.8], 1.3 (95% CI 1.0, 1.8), 1.4 (95% CI 0.9, 2.2) and 2.2 (95% CI 1.3, 3.5) times higher for the four drugs, respectively, at 100 compared with 50% predicted FEV1.
The higher plasma concentrations of inhaled corticosteroids in patients with a higher FEV1% predicted suggests that, for any given dose, these patients will be at greater risk of developing adverse systemic effects with long-term use.