Bo Jiang1, Zourong Ruan1, Jinliang Chen1, Honggang Lou1, Rong Shao1, Fang Jin2, Huahao Shen1. 1. a Center of Clinical Pharmacology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University , Hangzhou , China ; 2. b Shanghai Fronthealth Pharmaceutical Technology Co, Ltd , Shanghai , China.
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 AUC0-0.33 h, AUC0-24 h and Cmax 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 AUC0-0.33 h, 227.2 (89.9) pg·h/ml; AUC0-24 h, 2551.9 (1008.0) pg·h/ml; Cmax, 801.3 (307.3) pg/ml and t1/2, 5.14(1.36) h. Those of the test drug were AUC0-0.33 h, 244.0 (104.4) pg·h/ml; AUC0-24 h, 2664.4 (1081.8) pg·h/ml; Cmax, 873.7 (374.4) pg/ml, t1/2, 5.29 (1.23) h. The median value for Tmax was 0.25 h for both formulations. The 90% confidence intervals for the AUC0-0.33 h, AUC0-24 h and Cmax 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.
RCT Entities:
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 AUC0-0.33 h, AUC0-24 h and Cmax 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 AUC0-0.33 h, 227.2 (89.9) pg·h/ml; AUC0-24 h, 2551.9 (1008.0) pg·h/ml; Cmax, 801.3 (307.3) pg/ml and t1/2, 5.14(1.36) h. Those of the test drug were AUC0-0.33 h, 244.0 (104.4) pg·h/ml; AUC0-24 h, 2664.4 (1081.8) pg·h/ml; Cmax, 873.7 (374.4) pg/ml, t1/2, 5.29 (1.23) h. The median value for Tmax was 0.25 h for both formulations. The 90% confidence intervals for the AUC0-0.33 h, AUC0-24 h and Cmax 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.