NAC
NAC, an amino acid. Deacetylated in enterocytes/liver to cysteine — the rate-limiting substrate for glutathione (γGlu-Cys-Gly) synthesis. Also… Oral half-life 6 h.
Deacetylated in enterocytes/liver to cysteine — the rate-limiting substrate for glutathione (γGlu-Cys-Gly) synthesis. Also acts directly as a free-thiol antioxidant and disrupts disulfide bonds in airway mucin glycoproteins (mucolytic action). Clinically the antidote for acetaminophen-induced hepatotoxicity by restoring hepatic GSH consumed in NAPQI detoxification.
PK: THE VOLUME WAS THE SOLVER DEFAULT, THE BIOAVAILABILITY MATCHED NEITHER ARM, AND THE PAPER REPORTS TWO OF EVERYTHING. Its citation measures reduced and TOTAL N-acetylcysteine separately: "Reduced NAC had a volume of distribution (VSS) of 0.59 l.kg-1 and a plasma clearance of 0.84 l.h-1.kg-1 ... The oral bioavailability was 4.0%" against "its volume of distribution (VSS) was 0.47 l.kg-1 and its plasma clearance was 0.11 l.h-1.kg-1 ... Oral bioavailability of total NAC was 9.1%". The stored half-life of 6 h identifies the TOTAL arm ("5.58 h after intravenous administration and 6.25 h after oral"), so that is the arm the rest must come from — AND THE STORED BIOAVAILABILITY OF 0.07 IS NEITHER 4.0 NOR 9.1, sitting between them like a blend of two arms. It moves to the verbatim total-NAC figure. THE VOLUME IS DERIVED AND DECLARED: the verbatim steady-state volume paired with the terminal half-life asserts a clearance half the paper own, the usual Vss-against-terminal mismatch, so the stored value is that verbatim clearance over the stored rate and exposure now reproduces the paper.
Pharmacokinetics
- Oral — t½ 6 h · F 9% · Vd 66.7 L
- IV — t½ 6 h · F 100% · Vd 66.7 L
Related compounds
- Glycine — synergistic
- Nitroglycerin / nitrates — caution
- Cysteine — synergistic
- N-Acetylcysteine Amide — synergistic
Sources: PMID:3360052, PMID:3127076