TUSSMUCO Effervescent tablet Ref.[50573] Active ingredients: Acetylcysteine

Absorption

Following oral administration, N-acetylcysteine is rapidly and almost completely absorbed and metabolised in the liver to cysteine (the pharmacologically active metabolite), diN-acetylcysteine, cysteine and further mixed disulphides.

Distribution

Due to the high first-pass effect, the bioavailability of orally administered Nacetylcysteine is very low (approximately 10%). In humans, maximum plasma concentrations are achieved after 1 to 3 hours with the maximum plasma concentration of the metabolite cysteine in the range of approximately 2 µmol/L. The protein binding of N-acetylcysteine was determined to be about 50%.

Biotransformation

N-acetylcysteine and its metabolites occur in three different forms in the organism: partially in free form, partially bound to proteins via labile disulphide bonds and partially as incorporated amino acid. N-acetylcysteine is excreted almost exclusively in the form of inactive metabolites (inorganic sulphates, di-acetylcysteine) via the kidneys. The plasma half-life of N-acetylcysteine is approximately 1 hour and is mainly determined by the rapid hepatic biotransformation. Impaired hepatic function therefore leads to prolonged plasma half-lives of up to 8 hours.

Elimination

Pharmacokinetic studies with intravenous administration of N-acetylcysteine revealed a distribution volume of 0,47 L/kg (in total) or 0,59 L/kg (reduced N-acetylcysteine); the plasma clearance was determined to be 0,11 L/h/kg (in total) and 0,84 L/h/kg (reduced N-acetylcysteine), respectively. The elimination half-life after intravenous administration is 30 to 40 minutes while excretion follows three-phase kinetics (alpha, beta and terminal gamma phase).

N-acetylcysteine crosses the placenta and is detected in cord blood. No information is available regarding excretion in breast milk.

No knowledge is available concerning the behaviour of N-acetylcysteine at the bloodbrain barrier in humans.