Pharmacology: ERDOMED (erdosteine) acts pharmacologically as a fluidifying agent of bronchial mucus.
Pharmacodynamics: Pharmacotherapeutic Group: medicines for cough and cold diseases. ATC Code: R05CB15.
Mechanism of action/pharmacodynamic effects: Erdosteine, active ingredient of ERDOMED, in addition to its mucolytic properties on bronchial mucus thus facilitating expectoration, shows effects in antagonizing the local formation of free radicals and inhibiting the activity of the elastase enzyme.
Pharmacological studies have demonstrated that erdosteine does not possess these properties as such, but it is active only after metabolization. In fact, the SH groups, to which the activity is ascribed, are chemically used and become free only after metabolization or in alkaline environment. This property guarantees a good palatability with no bad taste and mercaptanic regurgitations and a good gastric tolerability.
Pharmacokinetics: Absorption: Erdosteine is rapidly absorbed after oral administration. After administration of a single dose of 900mg, the peak plasma concentration of erdosteine (Cmax) - 1.26 ± 0.23 mcg/ml - was reached 1.18 ± 0.26 hour after administration (Tmax), while N-thiodiglycolyl-homocysteine (Met-1) showed a Cmax of 3.46 mcg/ml and Tmax of 1.48 hour. The plasma concentrations of erdosteine increase in a dose-dependent manner. Plasma concentrations of Met-1 also increase with the dose, but not as proportionally as in the case of unchanged erdosteine. These findings may suggest a reduced metabolism, but not a reduced absorption, with increasing erdosteine doses. Food intake slightly delays the rate of absorption, without affecting the extent of absorption.
Distribution: Pharmacologically active concentrations of both erdosteine and Met-1 were found in bronchoalveolar lavage.
Metabolism: Erdosteine undergoes first-pass metabolism to its biologically active metabolite, Met-1, the only metabolite found in humans.
Elimination: The elimination half-life is 1.46 hour for erdosteine and 1.62 hour for Met-1. In urine, only Met-1 and sulphates were found, faecal elimination is negligible. No accumulation or change in the metabolism of erdosteine and Met-1 has been observed after oral administration of 600 to 900 mg daily for 8 days.
Special populations: Age does not affect the PK profile of erdosteine.
No adjustment of the posology seems to be necessary in patients affected by renal failure with creatinine clearance between 25 and 40 ml/min. No data are available in patients with creatinine clearance < 25 ml/min, therefore, the use of erdosteine is not recommended in these patients.
No data are available in patients suffering from severe liver failure, therefore the use of erdosteine is not recommended in these patients.
Toxicology: Preclinical safety data: Acute toxicity: LD (mouse, rat per os) > 5,000 mg/kg;
LD (rat i.p.) > 5,000 mg/kg;
LD (mouse i.v.) > 3,500 mg/kg.
Toxicity after long-term administration: Rat (per os, 26 weeks) absence of toxicity up to 1,000 mg/kg;
Dog (per os, 26 weeks) absence of toxicity up to 200 mg/kg.
Fetal toxicity: Rat per os absence of toxicity up to 1,000 mg/kg;
Rabbit per os absence of toxicity up to 250 mg/kg.