Pharmacokinetic properties of a drug, and selection and correct usage of an appropriate delivery device, are factors that can affect the outcome of inhaled therapy. The use of nebulization on can overcome problems that are associated with other delivery systems used for inhalation therapy. The objective of this open, randomized, single-dose study was to compare the systemic exposure and safety of beclometasone cipropionate (BDP) suspension for nebulization with BDP via metered-dose inhaler (MDI) in healthy subjects. Following a run-in period to assess basal 24-h serum cortisol levels and cortisol urinary excretion, 12 healthy males were administered BDP 1600 μg given via MDI and were then randomized to receive a single dose of either 1600 μg ( n=6) or 3200 μg BDP ( n=6) suspension for nebulization given via a nebulizer. Results with respect to systemic exposure to beclometasone-17-monopropionate (B17MP) (the active metabolite of BDP) and systemic effects on the hypothalamic-pituitary-adrenal (HPA) axis were determined by evaluation of a number of pharmacokinetic parameters for plasma B17MP and serum and urinary coritsol, respectively. A statistically significantly greater peak plasma concentration (C max) of B17MP was reported with BDP via MDI (1587 pg ml −1) compared with BDP 1600 μg (455 pg ml −1) and BDP 3200 μg suspensions for nebulization (758 pg ml −1), and was achieved more rapidly (T max) (1 · 3 h, 3 h, and 2 · 5 h, respectively). In addition, elimination half-life (t 1 2 el) was statistically significantly shorter with BDP via MDI (4·6 h) than with both dosages of BDP suspensions for nebulization (7·4 h and 6·3 h with 1600 μg and 3200 μg, respectively), as was mean residence time (MRT) (5·4 h, 11·1 h, and 10·0 h, respectively). Total systemci exposure to B17MP (as determined by the area under the concentration-time curve: AUC ∞) was comparable for BDP via MDI (6883 pg ml −1h −1) and BDP 3200 μg suspension for nebulization (8201 pg ml −1h −1), but significantly greater than with BDP 1600 μg suspension for nebulization (4870 pg ml −1; P<0·05 vs BDP via MDI). All treatments were well tolerated, and no significant differences were found between them with respect to the serum or urinary cortisol pharmacokinetic parameters assessed. In conclusion, the results of this study demonstrate that BDP suspension for nebulization 3200 μg given via a nebulizer and BDP 1600 μg given via an MDI are equivalent in terms of systemic exposure to B17MP and systemic effects on the HPA axis, with BDP suspension for nebulization having a potentially more prolonged activity. It confirms that use of a double dose of BDP suspension for nebulization administered by nebulizer compared with BDP given via metered-dose inhalation is justified and poses no risk with regard to safety.
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