C Godfrey1, H Buck, S Ellis. 1. Simbec Research Ltd, Merthyr Tydfil Industrial Park, Merthyr Tydfil, Mid Glamorgan, UK.
Abstract
OBJECTIVE: To compare the pharmacokinetic profile and bioavailability of budesonide after inhalation from the Clickhaler® dry powder inhaler with the Turbuhaler® as standard. DESIGN: Randomised, placebo-controlled, double-blind, double-dummy, crossover pilot study. SUBJECTS:Six healthy adult males aged 19 to 44 years (mean age 28 ± 9 years). METHODS: Each subject received budesonide 1000μg from the Clickhaler® or Turbuhaler® inhaler devices, and oral charcoal was administered to block gastrointestinal absorption. Plasma levels of budesonide and cortisol were determined at timepoints up to 8 hours postdose. Cortisol was also determined 24 hours postdose. RESULTS: The ratio of the plasma budesonide area under the concentration-time curve (AUC) calculated to 8 hours for the Clickhaler® to Turbuhaler® was 1.17 [90% confidence interval (CI) 0.90 to 1.54], indicating that pulmonary bioavailability was similar following inhalation from the two devices. Likewise, the time to the highest plasma concentration and maximum plasma concentration of budesonide following delivery from the Clickhaler® were similar to those following delivery of budesonide from the Turbuhaler®, with ratios of 0.95 (90% CI 0.51 to 1.77) and 1.14 (90% CI 0.76 to 1.72), respectively. The corresponding ratio for plasma cortisol AUC was 1.03 (90% CI 0.77 to 1.39). CONCLUSION:Budesonide Clickhaler® and budesonide Turbuhaler® dry powder inhalers demonstrated similar pharmacokinetic profiles, pulmonary bioavailability and systemic activity. As this was a small pilot study, it was not possible to determine the clinical implications of these results, but they suggest that the Clickhaler® and the Turbuhaler® achieve similar drug delivery.
RCT Entities:
OBJECTIVE: To compare the pharmacokinetic profile and bioavailability of budesonide after inhalation from the Clickhaler® dry powder inhaler with the Turbuhaler® as standard. DESIGN: Randomised, placebo-controlled, double-blind, double-dummy, crossover pilot study. SUBJECTS: Six healthy adult males aged 19 to 44 years (mean age 28 ± 9 years). METHODS: Each subject received budesonide 1000μg from the Clickhaler® or Turbuhaler® inhaler devices, and oral charcoal was administered to block gastrointestinal absorption. Plasma levels of budesonide and cortisol were determined at timepoints up to 8 hours postdose. Cortisol was also determined 24 hours postdose. RESULTS: The ratio of the plasma budesonide area under the concentration-time curve (AUC) calculated to 8 hours for the Clickhaler® to Turbuhaler® was 1.17 [90% confidence interval (CI) 0.90 to 1.54], indicating that pulmonary bioavailability was similar following inhalation from the two devices. Likewise, the time to the highest plasma concentration and maximum plasma concentration of budesonide following delivery from the Clickhaler® were similar to those following delivery of budesonide from the Turbuhaler®, with ratios of 0.95 (90% CI 0.51 to 1.77) and 1.14 (90% CI 0.76 to 1.72), respectively. The corresponding ratio for plasma cortisol AUC was 1.03 (90% CI 0.77 to 1.39). CONCLUSION:Budesonide Clickhaler® and budesonide Turbuhaler® dry powder inhalers demonstrated similar pharmacokinetic profiles, pulmonary bioavailability and systemic activity. As this was a small pilot study, it was not possible to determine the clinical implications of these results, but they suggest that the Clickhaler® and the Turbuhaler® achieve similar drug delivery.