Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1       Pharmacodynamic properties

Pharmacotherapeutic group: Mucolytics
ATC code: R05 CB01
Acetylcysteine is a derivative of the amino acid cysteine. Acetylcysteine has a secretolytic and secreto-mo- torial effect in the area of the bronchial tract. It is suspected of bursting the connection disulfide bridges between the mucopolysaccharide fibres and exercising a depolymerising effect on DNA fibres (in the purulent mucus). Thanks to this mechanism, the viscosity of the mucus is suspected to be reduced.
An alternative mechanism of acetylcysteine is alleged to be based on the ability of its reactive SH group to bind and thus to detoxify chemical radicals.
Further, acetylcysteine contributes to glutathione synthesis, which is important for the detoxification of noxae. This explains its effect as an antidote in paracetamol intoxications.
A protective effect in prophylactic administration of acetylcysteine on the frequency and severity of bacterial exacerbations in patients with chronic bronchitis/cystic fibrosis has been described.

Pharmacokinetic Properties

5.2       Pharmacokinetic properties

Following oral administration, acetylcysteine is resorbed quickly and practically completely and metabolised in the liver to form cysteine, the pharmacologically active metabolite, and diacetylcystine, cystine and further mixed disulfides. As a result of the high first-pass effect, bio-availability of orally administered acetylcysteine is very low (approx. 10%). In humans, the maximum plasma concentrations are reached after 1-3 hours, the maximum plasma concentration of the metabolite cystine being in the range of about 2 µmol/l. The protein binding of acetylcysteine was determined at about 50%.
Acetylcysteine and its metabolites occur in the organism in three differing forms: partly in a free form, partly bound to protein via instable disulfide bridges and partly as an integrated amino acid. Excretion is almost exclusively in the form of inactive metabolites (inorganic sulphates, diacetylcystine) via the kidneys. The plasma half-life of acetylcysteine is about 1 hour and is mainly determined by the fast hepatic biotransforma- tion. A limitation of the hepatic function therefore leads to prolonged plasma half-lives of up to 8 hours.
Pharmacokinetic examinations with intravenous administration of acetylcysteine resulted in a distribution volume of 0.47 l/kg (total) and 0.59 l/kg (reduced), plasma clearance being determined with 0.11 l/h/kg (total) and 0.84 l/h/kg (reduced). The elimination half-life after i.v. administration is 30-40 min., excretion following three-phased kinetics (alpha, beta and terminal gamma phase).
N-acetylcysteine passes the placenta and can be detected in the umbilical blood. There is no information about excretion into the mother's milk.
No information is available on the behaviour of acetylcysteine on the blood-brain barrier for application in human beings.