Pharmacokinetic and pharmacodynamic comparison of hydrofluoroalkane and chlorofluorocarbon formulations of budesonide
Bibliographic record
Abstract
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Chlorofluorocarbons (CFCs) have been implicated in damage to the ozone layer, and are due to be phased out in accordance with the Montreal Protocol. • Hydrofluoroalkane‐134a (HFA) has been found to act as an adequate propellant for pressurized metered‐dose inhaler delivery systems without the same deleterious environmental effects. WHAT THIS STUDY ADDS • This paper presents data from both steady‐state pharmacokinetic and pharmacodynamic assessments of HFA vs. CFC pressurized metered‐dose inhaler formulations of budesonide. It demonstrates that they are therapeutically equivalent in terms of relative lung bioavailability, airway efficacy and systemic effects. AIMS A hydrofluoroalkane formulation of budesonide pressurized metered‐dose inhaler has been developed to replace the existing chlorofluorocarbon one. The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic characteristics of both formulations. METHODS Systemic bioavailability and bioactivity of both hydrofluoroalkane and chlorofluorocarbon pressurized metered‐dose inhaler formulations at 800 µg twice daily was determined during a randomized crossover systemic pharmacokinetic/pharmacodynamic study at steady state in healthy volunteers. Measurements included the following: plasma cortisol AUC 24h [area under the concentration‐time curve (0–24 h)], budesonide AUC 0–12h and C max . Clinical efficacy was determined during a randomized crossover pharmacodynamic study in asthmatic patients receiving 200 µg followed by 800 µg budesonide via chlorofluorocarbon or hydrofluoroalkane pressurized metered‐dose inhaler each for 4 weeks. Methacholine PC 20 (primary outcome), exhaled nitric oxide, spirometry, peak expiratory flow and symptoms were evaluated. RESULTS In the pharmacokinetic study, there were no differences in cortisol, AUC 0–12h [area under the concentration‐time curve (0–12 h)], T max (time to maximum concentration) or C max (peak serum concentration) between the hydrofluoroalkane and chlorofluorocarbon pressurized metered‐dose inhaler. The ratio of budesonide hydrofluoroalkane vs. chlorofluorocarbon pressurized metered‐dose inhaler for cortisol AUC 24h was 1.02 (95% confidence interval 0.93–1.11) and budesonide AUC 0–12h was 1.03 (90% confidence interval 0.9–1.18). In the asthma pharmacodynamic study, there was a significant dose response ( P < 0.0001) for methacholine PC 20 (provocative concentration of methacholine needed to produce a 20% fall in FEV 1 ) with a relative potency ratio of 1.10 (95% confidence interval 0.49–2.66), and no difference at either dose. No significant differences between formulations were seen with the secondary outcome variables. CONCLUSIONS Hydrofluoroalkane and chlorofluorocarbon formulations of budesonide were therapeutically equivalent in terms of relative lung bioavailability, airway efficacy and systemic effects.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".