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Keywords:

  • airflow obstruction;
  • asthma;
  • inhaled corticosteroid;
  • pharmacology

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 (= 0.05), 0.33 (= 0.08), 0.25 (= 0.2) and 0.52 (= 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.

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.