Acetylcysteine - How It Works
Clinical pharmacology details from the US FDA-approved label: how Acetylcysteine works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose. Acetaminophen doses of 150 mg/kg or greater have been associated with hepatotoxicity. Acetylcysteine probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite of acetaminophen.
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose.
Acetaminophen doses of 150 mg/kg or greater have been associated with hepatotoxicity.
Acetylcysteine probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and thus detoxification of, the reactive metabolite of acetaminophen.
12.3 Pharmacokinetics After a single intravenous dose of acetylcysteine, the plasma concentration of total acetylcysteine declined in a poly-exponential decay manner with a mean terminal half-life (T 1/2 ) of 5.6 hours.
The mean clearance (CL) for acetylcysteine was 0.11 liter/hr/kg and renal CL constituted about 30% of the total CL.
Distribution : The steady-state volume of distribution (Vd ss ) following administration of an intravenous dose of acetylcysteine was 0.47 liter/kg.
The protein binding of acetylcysteine ranges from 66 to 87%.
Elimination Metabolism: Acetylcysteine (i.e., N -acetylcysteine) is postulated to form cysteine and disulfides (N,N-diacetylcysteine and N -acetylcysteine).
Cysteine is further metabolized to form glutathione and other metabolites.
Excretion After a single oral dose of [ 35 S]-acetylcysteine 100 mg, between 13 to 38% of the total radioactivity administered was recovered in urine within 24 hours.
In a separate study, renal clearance was estimated to be approximately 30% of total body clearance.
Specific Populations : Hepatic Impairment: Following a 600 mg intravenous dose of acetylcysteine to subjects with mild (Child Pugh Class A, n=1), moderate (Child-Pugh Class B, n=4) or severe (Child-Pugh Class C; n=4) hepatic impairment and 6 healthy matched controls, mean T 1/2 increased by 80%.
Also, the mean CL decreased by 30% and the systemic acetylcysteine exposure (mean AUC) increased 1.6-fold in subjects with hepatic impairment compared to subjects with normal hepatic function.
These changes are not considered to be clinically meaningful.
Renal Impairment Hemodialysis may remove some of total acetylcysteine.
Pharmacokinetics
12.3 Pharmacokinetics After a single intravenous dose of acetylcysteine, the plasma concentration of total acetylcysteine declined in a poly-exponential decay manner with a mean terminal half-life (T 1/2 ) of 5.6 hours. The mean clearance (CL) for acetylcysteine was 0.11 liter/hr/kg and renal CL constituted about 30% of the total CL. Distribution : The steady-state volume of distribution (Vd ss ) following administration of an intravenous dose of acetylcysteine was 0.47 liter/kg. The protein binding of acetylcysteine ranges from 66 to 87%. Elimination Metabolism: Acetylcysteine (i.e., N -acetylcysteine) is postulated to form cysteine and disulfides (N,N-diacetylcysteine and N -acetylcysteine). Cysteine is further metabolized to form glutathione and other metabolites. Excretion After a single oral dose of [ 35 S]-acetylcysteine 100 mg, between 13 to 38% of the total radioactivity administered was recovered in urine within 24 hours. In a separate study, renal clearance was estimated to be approximately 30% of total body clearance. Specific Populations : Hepatic Impairment: Following a 600 mg intravenous dose of acetylcysteine to subjects with mild (Child Pugh Class A, n=1), moderate (Child-Pugh Class B, n=4) or severe (Child-Pugh Class C; n=4) hepatic impairment and 6 healthy matched controls, mean T 1/2 increased by 80%. Also, the mean CL decreased by 30% and the systemic acetylcysteine exposure (mean AUC) increased 1.6-fold in subjects with hepatic impairment compared to subj