Pharmacokinetic properties and bioequivalence of orally inhaled salbutamol in healthy Chinese volunteers

Abstract

Context: Salbutamol is a short-acting β₂-adrenergic receptor agonist that has been used for many years for relief of bronchospasm. However, studies on the pharmacokinetic profile of orally inhaled salbutamol doses used in clinical practice have not yet been reported in Chinese subjects.

Objective: The aim of this study was to compare the pharmacokinetics and evaluate the bioequivalence of two orally inhaled salbutamol formulations.

Materials and methods: A single-dose randomized fasting two-period, two-treatment and two-sequence crossover open-label bioequivalence study was conducted in 24 healthy Chinese adult male volunteers, with a 1-week washout period between treatments. Plasma concentrations of salbutamol were determined using liquid chromatography coupled to tandem mass spectrometry. Pharmacokinetic parameters, including AUC_0–0.33 h, AUC_0–24 h and C_max were calculated and the 90% confidence intervals of the ratio (test/reference) pharmacokinetic parameters were obtained by analysis of variance on logarithmically transformed data.

Results: The mean (SD) pharmacokinetic parameters of the reference drug were AUC_0–0.33 h, 227.2 (89.9) pg·h/ml; AUC_0–24 h, 2551.9 (1008.0) pg·h/ml; C_max, 801.3 (307.3) pg/ml and t_1/2, 5.14(1.36) h. Those of the test drug were AUC_0–0.33 h, 244.0 (104.4) pg·h/ml; AUC_0–24 h, 2664.4 (1081.8) pg·h/ml; C_max, 873.7 (374.4) pg/ml, t_1/2, 5.29 (1.23) h. The median value for T_max was 0.25 h for both formulations. The 90% confidence intervals for the AUC_0–0.33 h, AUC_0–24 h and C_max were in the range of 0.892–1.208, 0.876–1.195 and 0.911–1.203, respectively.

Conclusion: This single-dose study found that the test and reference products met the regulatory criteria for bioequivalence of China in healthy Chinese volunteers.

Keywords:

• β2-adrenergic receptor
• inhalation administration
• lung deposition
• particle size profile
• systemic absorption

Acknowledgements

The authors would like to thank the study sponsor (Yangzhousanyao Pharmaceutical Co., Ltd., Jiangsu, China).

Disclosure statement

The authors report no declarations of interest. The authors alone are responsible for the content and writing of this article.

Funding information

This research is supported by the National Nature Science Foundation of China (81400025).