Investigation of a potential drug-drug interaction between salbutamol and ambroxol and bioequivalence of a new fixed-dose combination containing these two drugs in healthy Chinese subjects

摘要

Objectives: The aims of the study were to investigate the potential drug-rug interaction between salbutamol and ambroxol, the bioequivalence of the new fixed-dose combination containing salbutamol and ambroxol compared with co-administration of the two separate formulations, and to describe the safety and tolerability of the fixed-dose combination formulation in healthy Chinese volunteers. Materials and methods: An open-label, single-dose, four-treatment, four-period crossover study for evaluation of drug-drug interaction and bioequivalence (n = 24) was performed. Each participant received salbutamol 4 mg, ambroxol 15 mg, salbutamol 4 mg co-administered with ambroxol 15 mg or fixed-dose combination formulation (salbutamol 4 mg and ambroxol 15 mg). Plasma concentrations of two analytes were determined with the use of validated LC-MS/MS method. Safety and tolerability were assessed by recording adverse events. Results: Co-administration of salbutamol and ambroxol was not associated with a significant influence on single salbutamol or ambroxol pharmacokinetics. After statistical comparisons of log-transformed C-max and AUC of salbutamol and ambroxol between fixed-dose combination and concomitant treatments, all 90% confidence intervals of geometric mean ratios were within the predefined equivalence range of 80 - 125%. No serious adverse events were reported, and all treatments were safe and well tolerated in Chinese healthy subjects. Conclusion: There were no significant drug-drug pharmacokinetic interactions between salbutamol and ambroxol after oral administration. The new formulation was bioequivalent to the co-administration of two drugs in separate dosage forms.