Pharmacokinetics and systemic effects of inhaled fluticasone propionate in chronic obstructive pulmonary disease

Authors


Dr S. D. Singh, Medicines Evaluation Unit, North-west Lung Research Centre, South Manchester University Hospital Trust, Southmoor Road, Wythenshawe, Manchester M23 9LT, UK. Fax: + 44 16 1291 5020; E-mail: dave_sd@hotmail.com

Abstract

Aims  We have previously shown that the systemic exposure to inhaled fluticasone propionate (FP) is reduced in asthmatics compared with healthy subjects. We have now compared its pharmacokinetics in patients suffering from chronic obstructive pulmonary disease (COPD, n = 10) and matched healthy subjects (n = 13).

Methods  A double-blind, randomized, cross-over study design was used. Plasma FP and serum cortisol were measured for 12 h after subjects received hydrofluoroalkane FP 1000 µg day−1 inhaled (via an MDI and spacer) for 7 days and following a single 1000-µg intravenous dose.

Results  The pharmacokinetics differed in the two groups. After inhalation, geometric least square means were significantly lower in the COPD group for the plasma AUC (1961 vs 2996 pg ml−1 h−1 for COPD and controls, respectively; P = 0.03) and the Cmax (235 vs 421 pg ml−1 for COPD and controls, respectively; P = 0.03). Suppression of serum cortisol concentration over 12 h was greater in healthy controls. Weighted mean serum cortisol concentration (nmol l−1) in healthy subjects and COPD was 93 and 170, respectively (P = 0.03). The intravenous pharmacokinetic parameters for FP were comparable in the two groups, resulting in similar suppression of serum cortisol.

Conclusions  We conclude that the altered pharmacokinetics of inhaled fluticasone propionate in COPD caused less hypothalamic–pituitary–adrenal suppression than in healthy controls. This is further evidence that the systemic effects of inhaled corticosteroids should be assessed in patients and not healthy subjects.

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