AIMS: The aim of this study was to compare lung deposition of budesonide administered from two dry powder inhalers, Giona Easyhaler 200 microg/dose and Pulmicort Turbuhaler 200 microg/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 microg (5 x 200 microg) 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, infinity)) 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, infinity) fell within the limits of 0.8-1.25. RESULTS: The mean AUC(0,infinity) 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, infinity) 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 microg/dose and Pulmicort Turbuhaler 200 microg/dose dry powder inhalers is equivalent. The charcoal block used to prevent GI absorption of swallowed budesonide was found to be effective.
RCT Entities:
AIMS: The aim of this study was to compare lung deposition of budesonide administered from two dry powder inhalers, Giona Easyhaler 200 microg/dose and Pulmicort Turbuhaler 200 microg/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 microg (5 x 200 microg) 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, infinity)) 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, infinity) fell within the limits of 0.8-1.25. RESULTS: The mean AUC(0,infinity) 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, infinity) 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 microg/dose and Pulmicort Turbuhaler 200 microg/dose dry powder inhalers is equivalent. The charcoal block used to prevent GI absorption of swallowed budesonide was found to be effective.
Authors: J H Toogood; C W Frankish; B H Jennings; J C Baskerville; O Borga; N M Lefcoe; S A Johansson Journal: J Allergy Clin Immunol Date: 1990-05 Impact factor: 10.793