Summary of the Compound N-Acetylcysteine
Drug indication NAC is used mainly as a mucolytic and in the management of acetaminophen (paracetamol) overdose.
Chemical structure	Molecular formula C5H9NO3S		Synonyms
			▪N-Acetyl-cysteine; ▪Acetylcysteine; ▪N-Acetylcysteine; ▪NAC; ▪Ac-Cys-OH; ▪616–91-1.
	pKa 3.24: –COOH and 9.5: –SH
Molecular weight 163.2 g/mol	Protein binding 66–97% (usually to albumin)		WHO essential medicines Antidotes and other substances used in poisonings.
Drug classes	Therapeutic uses		Taste Characteristic sour taste
▪Antidotes; ▪Toxicological emergency.	▪Antiviral agents; ▪Expectorants; ▪Free-radical scavengers.
			Color/Form White crystalline powder
			Odor Slight acetic odor
Drug warnings
▪Anaphylactoid reactions, such as rash, hypotension, wheezing, and/or dyspnea, have been reported after administration of parenteral NAC; ▪Anaphylactoid reactions can be more severe and even cause death in patients with asthma; ▪Skin rash, urticaria, and pruritus are the most reported adverse effects after intravenous NAC administration; ▪Acute flushing and erythema are less serious adverse reactions after intravenous administration of NAC; ▪Chest tightness and bronchoconstriction have been reported after the use of NAC; ▪Bronchospasm clinically induced by NAC is rare; ▪Increased airway obstruction can occur after oral NAC inhalation; ▪Gastrointestinal symptoms, including nausea and vomiting, are more frequent and may occur after oral administration of NAC.
Absorption
▪Bioavailability is 6–10% following oral administration and less than 3% following topical administration; ▪Serum concentrations after intravenous administration of an initial loading dose of 150 mg/kg over 15 min are about 500 mg/L.
Metabolism
▪Deacetylated by the liver to cysteine and subsequently metabolized; ▪After oral inhalation or intratracheal instillation, most of the administered drug appears to participate in the sulfhydryl disulfide reaction, while the rest is absorbed by the pulmonary epithelium, deacetylated by the liver to cysteine to be metabolized.
Half-life	Clearance	Volume of distrib	Excretion
▪Adults—5.6 h; ▪Neonates—11 h.	0.11 L/h/kg	ution 0.47 L/kg	▪13–38% (urine); ▪3% (feces).
Dosage forms		Overdosage
▪Solution for inhalation; ▪Intravenous injection; ▪Oral solution; ▪Effervescent tablets; ▪Capsules; ▪Tablets; ▪Powder; ▪Granule; ▪Liquid; ▪Ocular solution.		Single intravenous doses of NAC that were lethal: ▪1000 mg/kg in mice; ▪2445 mg/kg in rats; ▪1500 mg/kg in guinea pigs; ▪1200 mg/kg in rabbits; ▪ 500 mg/kg in dogs. Symptoms of acute toxicity were ataxia, hypoactivity, labored respiration, cyanosis, loss of righting reflex, and convulsions.
Drug–drug interactions
▪NAC can reduce the excretion of various drugs (e.g., pravastatin, valsartan, erythromycin, torasemide, lovastatin, liothyronine, digoxin, cerivastatin, raloxifene, caspofungin, enalapril, simvastatin, penicillamine); ▪The serum concentration of eluxadoline can be increased when combined with NAC; ▪The therapeutic efficacy of NAC can be decreased when used in combination with oxytetracycline, trypsin, or tetracycline.
Adapted from PubChem (2021) [31] and DrugBank (2021) [32].