Authors: Mortimer, Kevin J.; Harrison, Tim W.; Tang, Yufei; Wu, Kai; Lewis, Sarah; Sahasranaman, Srikumar; Hochhaus, Gunther; Tattersfield, Anne E.

Source: British Journal of Clinical Pharmacology, Volume 62, Number 4, October 2006 , pp. 412-419(8)

Publisher: Wiley-Blackwell

Abstract:

Aims

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. Methods

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. Results

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 FEV_1. Conclusion

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.

Keywords: airflow obstruction; asthma; inhaled corticosteroid; pharmacology

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2125.2006.02712.x

Affiliations: 1: Department of Pharmaceutics, University of Florida, Gainesville, FL, USA

Publication date: 2006-10-01

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