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Equivalent lung deposition of budesonide in vivo : a comparison of dry powder inhalers using a pharmacokinetic method
Author(s) -
Lähelmä Satu,
Kirjavainen Merja,
Kela Marjo,
Herttuainen Jukka,
Vahteristo Mikko,
Silvasti Matti,
RankiPesonen Marjut
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2004.02238.x
Subject(s) - budesonide , pharmacokinetics , crossover study , dry powder inhaler , chemistry , cmax , oral administration , inhalation , medicine , pharmacology , chromatography , placebo , asthma , inhaler , anesthesia , alternative medicine , pathology
Aims The aim of this study was to compare lung deposition of budesonide administered from two dry powder inhalers, Giona ® Easyhaler ® 200 µg/dose and Pulmicort ® Turbuhaler ® 200 µg/dose by utilizing a pharmacokinetic method. Methods This was an open, randomized, crossover study in 33 healthy subjects. The study consisted of four treatment periods separated by at least 4 wash‐out days. Equivalence in lung deposition was assessed after a single inhaled 1000 µg (5 × 200 µg) dose of budesonide from Giona ® Easyhaler ® and from Pulmicort ® Turbuhaler ® . Concomitant oral charcoal administration (40 g) was used to prevent gastrointestinal (GI) absorption of budesonide. The efficacy of the charcoal was studied after oral administration of a budesonide 2 mg capsule. The subjects were trained to inhale the study drugs with controlled flow rates, which resulted in an equal pressure drop (4 kPa) across both inhalers. Venous blood samples for the determination of budesonide concentrations in plasma were drawn before and at predetermined time points up to 8 h after drug administration. Budesonide concentrations in plasma were determined using liquid chromatography‐tandem mass spectrometry. Several pharmacokinetic parameters were estimated, the area under the budesonide concentration in plasma vs time curve from dosing to infinity (AUC(0, ∞)) being the primary response variable. Equivalence in lung deposition was concluded if the 90% confidence interval (CI) for the Easyhaler ® : Turbuhaler ® ratio of AUC(0, ∞) fell within the limits of 0.8–1.25. Results The mean AUC(0,∞) value after Easyhaler ® treatment was 3.48 (standard deviation (SD) 0.93) ng ml −1 h and after Turbuhaler ® treatment 3.46 (1.13) ng ml −1 h. The Easyhaler ® : Turbuhaler ® AUC(0, ∞) ratio was 1.02 and the 90% CI was from 0.96 to 1.09. The mean C max values (SD) for budesonide in plasma after Easyhaler ® and Turbuhaler ® treatments were 1.22 (0.41) ng ml −1 and 1.29 (0.44) ng ml −1 , respectively. There was no statistically significant difference ( P = 0.39) between the median t max for Easyhaler ® (30 min) and Turbuhaler ® treatment (23 min). Charcoal impaired the GI absorption of budesonide by 96%. The occurrence of adverse events was similar during both treatments. Conclusions The results show that the lung deposition of budesonide from Giona ® Easyhaler ® 200 µg/dose and Pulmicort ® Turbuhaler ® 200 µg/dose dry powder inhalers is equivalent. The charcoal block used to prevent GI absorption of swallowed budesonide was found to be effective.