Ambroxyl Mechanism of Action

Pharmacology: Ambroxol Hydrochloride is a derivative of the mucolytic, bromhexine which has been found to possess secretolytic and mucokinetic properties. It acts by increasing the production of serum concentrations of the bronchial mucus-secreting glands in the respiratory tract. Through its pulmonary surfactant stimulating activity, Ambroxol Hydrochloride accelerates mucus transport, promoting expulsion of thick, tenacious secretions from the respiratory tract. During treatment with Ambroxol Hydrochloride, chronically inflamed bronchial mucosa tends to return to normal. The patients cough and sputum volumes are reduced; expectoration is facilitated; and breathing is eased considerably.
The good tolerability of Ambroxol Hydrochloride permits its long term use.
Pharmacokinetics: Absorption: Absorption of all immediate release oral forms of Ambroxol hydrochloride is rapid and complete, with dose linearity in the therapeutic range. Maximum plasma levels are reached within 1 to 2.5 hours following oral administration of the immediate-release formulation and after a median of 6.5 hours of the slow-release formulation. The absolute bioavailability after oral administration of 30 mg tablet of Ambroxol was found to be 79%.
Distribution: In the therapeutic range, plasma-protein binding was found to be approximately 90%. Distribution of Ambroxol hydrochloride from blood to tissue is rapid and pronounced, with the highest of the active substance found in the lungs. The volume of distribution following oral administration was estimated to be 552 L.
Metabolism and Elimination: About 30% of an orally administered dose is eliminated via first-pass metabolism. Studies in human liver microsomes have shown that CYP3A4 is responsible for the metabolism of Ambroxol. Ambroxol Hydrochloride is metabolized primarily in the liver by glucuronidation and some cleavage to dibromoanthranilic acid (approximately 10% of dose) aside from some minor metabolites. Ambroxol hydrochloride is eliminated with a terminal half-life of approximately 10 hours. Total clearance is in the range of 660 mL/min, with renal clearance accounting for approximately 83% of the total clearance.
Special Populations: In patients with hepatic dysfunction, elimination of Ambroxol hydrochloride is reduced, resulting in approximately 1.3 to 2-fold higher plasma levels. Due to the high therapeutic range of Ambroxol Hydrochloride, dose adjustments are not necessary.
Others: Age and gender were not found to affect the pharmacokinetics of Ambroxol Hydrochloride to a clinically relevant extent and thus there in no necessity for adjustment of dose regimens. Food was not found to influence the bioavailability of Ambroxol hydrochloride.