Bioequivalence of budesonide inhalation suspension with and without activated charcoal in healthy Chinese subjects: two randomized four-period crossover trials
- 1Department of Phase I Clinical Trial Center, Beijing Shijitan Hospital, Capital Medical University , ,
- 2Department of Allergy, Beijing Shijitan Hospital, Capital Medical University , ,
- 3Special Medical Services Department, Beijing Shijitan Hospital, Capital Medical University , ,
Abstract
Background: Demonstrating bioequivalence for locally acting inhaled products is challenging because systemic exposure may reflect both pulmonary absorption and gastrointestinal absorption of the swallowed fraction. Activated charcoal can suppress gastrointestinal uptake and may help interpret lung-derived exposure more directly.
Methods: Two open-label, randomized, single-dose, four-period crossover pharmacokinetic bioequivalence trials were conducted in healthy Chinese adults, one under non-block conditions and one under charcoal-block conditions. Thirty-six subjects were enrolled in each trial. In each period, subjects inhaled a single 1 mg dose of the test or reference budesonide inhalation suspension via a standardized jet nebulizer procedure, with a 5-day washout between periods. Plasma budesonide concentrations were measured for 15 h. The primary pharmacokinetic endpoints were Cmax, AUC0-t, and AUC0-inf, and bioequivalence was concluded if the 90% confidence intervals for the test/reference geometric mean ratios were within 80.00%–125.00%.
Results: Under both non-block and charcoal-block conditions, the 90% confidence intervals for Cmax, AUC0-t, and AUC0-inf met the predefined bioequivalence criteria. In exploratory between-cohort comparisons based on subject-level arithmetic summaries, activated-charcoal blockade was associated with numerically lower AUC values, whereas Cmax remained similar; however, nominal exploratory P values for Cmax, AUC0-t, and AUC0-inf were all >0.05 and were not used for confirmatory inference. These findings are consistent with, but do not establish, a predominant pulmonary contribution to systemic exposure after nebulization. Both formulations were well tolerated, and no serious adverse events were reported.
Conclusion: The test and reference budesonide inhalation suspension formulations were bioequivalent under both non-block and charcoal-block conditions. Exploratory between-cohort comparisons showed no statistically significant differences in Cmax, AUC0-t, or AUC0-inf based on nominal P values. The charcoal-related findings are consistent with, but do not establish, a predominant pulmonary contribution to systemic exposure after nebulization and should be interpreted cautiously because the conditions were evaluated in separate cohorts. Overall, the two studies provide supportive pharmacokinetic evidence for the evaluation of generic nebulized budesonide products.
Trial Registration: Clinical Trial Registration: Drug Clinical Trial Registration and Information Publicity Platform of the National Medical Products Administration of China, CTR20200344 and CTR20201473 (http://www.chinadrugtrials.org.cn/); Chinese Clinical Trial Registry, ChiCTR2000035173 (https://www.chictr.org.cn/).
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BibTeX
@article{li2026bioequivalence,
title = {{Bioequivalence of budesonide inhalation suspension with and without activated charcoal in healthy Chinese subjects: two randomized four-period crossover trials}},
author = {Yinjuan Li and Lu Qi and Rongxia Fan and Qian Zhang and Ju Liu and Xiaoqiang Cheng and Xinghe Wang},
journal = {Journal of pharmacy \& pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques},
year = {2026},
month = oct,
doi = {10.3389/jpps.2026.17048},
url = {https://europepmc.org/article/PMC/PMC13727514},
note = {CC BY},
}
RIS
TY - JOUR
TI - Bioequivalence of budesonide inhalation suspension with and without activated charcoal in healthy Chinese subjects: two randomized four-period crossover trials
AU - Yinjuan Li
AU - Lu Qi
AU - Rongxia Fan
AU - Qian Zhang
AU - Ju Liu
AU - Xiaoqiang Cheng
AU - Xinghe Wang
PY - 2026
DA - 2026/10/20
JO - Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques
DO - 10.3389/jpps.2026.17048
UR - https://europepmc.org/article/PMC/PMC13727514
AB - Background: Demonstrating bioequivalence for locally acting inhaled products is challenging because systemic exposure may reflect both pulmonary absorption and gastrointestinal absorption of the swallowed fraction. Activated charcoal can suppress gastrointestinal uptake and may help interpret lung-derived exposure more directly. Methods: Two open-label, randomized, single-dose, four-period crossover pharmacokinetic bioequivalence trials were conducted in healthy Chinese adults, one under non-block conditions and one under charcoal-block conditions. Thirty-six subjects were enrolled in each trial. In each period, subjects inhaled a single 1 mg dose of the test or reference budesonide inhalation suspension via a standardized jet nebulizer procedure, with a 5-day washout between periods. Plasma budesonide concentrations were measured for 15 h. The primary pharmacokinetic endpoints were Cmax, AUC0-t, and AUC0-inf, and bioequivalence was concluded if the 90% confidence intervals for the test/reference geometric mean ratios were within 80.00%–125.00%. Results: Under both non-block and charcoal-block conditions, the 90% confidence intervals for Cmax, AUC0-t, and AUC0-inf met the predefined bioequivalence criteria. In exploratory between-cohort comparisons based on subject-level arithmetic summaries, activated-charcoal blockade was associated with numerically lower AUC values, whereas Cmax remained similar; however, nominal exploratory P values for Cmax, AUC0-t, and AUC0-inf were all >0.05 and were not used for confirmatory inference. These findings are consistent with, but do not establish, a predominant pulmonary contribution to systemic exposure after nebulization. Both formulations were well tolerated, and no serious adverse events were reported. Conclusion: The test and reference budesonide inhalation suspension formulations were bioequivalent under both non-block and charcoal-block conditions. Exploratory between-cohort comparisons showed no statistically significant differences in Cmax, AUC0-t, or AUC0-inf based on nominal P values. The charcoal-related findings are consistent with, but do not establish, a predominant pulmonary contribution to systemic exposure after nebulization and should be interpreted cautiously because the conditions were evaluated in separate cohorts. Overall, the two studies provide supportive pharmacokinetic evidence for the evaluation of generic nebulized budesonide products. Trial Registration: Clinical Trial Registration: Drug Clinical Trial Registration and Information Publicity Platform of the National Medical Products Administration of China, CTR20200344 and CTR20201473 (http://www.chinadrugtrials.org.cn/); Chinese Clinical Trial Registry, ChiCTR2000035173 (https://www.chictr.org.cn/).
SN - 1482-1826
ER -