Work

Bioequivalence of budesonide inhalation suspension with and without activated charcoal in healthy Chinese subjects: two randomized four-period crossover trials

Year: 2026

Type: article

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 C max , AUC 0-t , and AUC 0-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 C max , AUC 0-t , and AUC 0-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 C max remained similar; however, nominal exploratory P values for C max , AUC 0-t , and AUC 0-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 C max , AUC 0-t , or AUC 0-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/ ).

Source: Journal of Pharmacy & Pharmaceutical Sciences

DOI: 10.3389/jpps.2026.17048