Duro-Tuss AX Chesty Cough Liquid Mechanism of Action

Pharmacology: Pharmacodynamics: Preclinically, ambroxol hydrochloride, has been shown to increase respiratory tract secretion. It enhances pulmonary surfactant production and stimulates ciliary activity. These actions result in improved mucus flow and transport (mucociliary clearance). Improvement of mucociliary clearance has been shown in clinical pharmacologic studies. Enhancement of fluid secretion and mucociliary clearance facilitates expectoration and eases cough. Patients in the ambroxol hydrochloride treatment group lost significantly fewer days through illness and had fewer days when they needed antibiotic therapy. Treatment with ambroxol hydrochloride also induced a statistically significant improvement of symptoms (difficulty of expectoration, cough, dyspnea, auscultatory signs) compared with placebo. A local anaesthetic effect of ambroxol hydrochloride has been observed in the rabbit eye model which may be explained by the sodium channel blocking properties. It was shown in vitro that ambroxol hydrochloride blocks cloned neuronal sodium channels; binding was reversible and concentration-dependent. Cytokine release from blood but also tissue-bound mononuclear and polymorphonuclear cells was found to be significantly reduced by ambroxol hydrochloride in vitro. In clinical studies in patients with sore throat, pharyngeal pain and redness was significantly reduced. Following the administration of ambroxol, antibiotic concentrations (amoxicilline, cefuroxime, erythromycin) in bronchopulmonary secretions and in the sputum are increased. Antiviral properties in in vitro studies and in animal models: In in vitro studies in human tracheal epithelial cells a reduction of rhinovirus (RV14) replication has been observed. In a mouse airway model, a reduction of Influenza A virus replication was observed with ambroxol pretreatment.
Pharmacokinetics: Absorption: Absorption of immediate release oral dosage forms of ambroxol hydrochloride is fast and complete, with dose linearity in the therapeutic range. Maximum plasma levels are reached within 1 to 2.5 hours after administration of the immediate-release formulation and after a median of 6.5 hours after administration of the slow-release formulation. Food was not found to have any effect on the bioavailability of ambroxol hydrochloride.
Distribution: Distribution of ambroxol hydrochloride from blood to tissue is rapid and pronounced, with the highest concentration of the active substance found in the lungs. The estimated volume of distribution after oral administration is 552 litres. In the therapeutic range, plasma protein binding is found to be approximately 90%.
Metabolism: About 30% of the orally administered dose is eliminated via first-pass metabolism.
Ambroxol hydrochloride is primarily metabolized in the liver through glucuronidation and cleavage to dibromanthranilic acid (approx. 10% of the dose). Studies in human liver microsomes have shown that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromoanthranilic acid.
Elimination: After 3 days of oral administration, ambroxol hydrochloride is eliminated renally, approx. 6% unchanged and approx. 26% in the form of its conjugates. The terminal elimination half-life of ambroxol hydrochloride is about 10 hours. Total clearance is in the range of 660 mL/min, with renal clearance accounting for approx. 8% of the total clearance. After 5 days an estimated 83% of total dose (radioactively marked) is eliminated with the urine.
Special patient groups: The elimination of ambroxol hydrochloride is reduced in patients with impaired liver function, resulting in plasma levels approx. 1.3 to 2 times higher. Due to the high therapeutic range of active substance, a dose adjustment is not necessary. Age and gender were not found to affect the pharmacokinetics of ambroxol hydrochloride to a clinically relevant degree. Therefore, deviating from the recommended dose is not necessary.