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Effect of antidotal N‐acetylcysteine on the pharmacokinetics of acetaminophen in dogs
Author(s) -
OMER V. E. V. ST.,
MOHAMMAD F. K.
Publication year - 1984
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.1984.tb00912.x
Subject(s) - pharmacokinetics , acetylcysteine , acetaminophen , chemistry , volume of distribution , saline , elimination rate constant , anesthesia , isotonic saline , pharmacology , medicine , oral administration , antidote , toxicity , antioxidant , biochemistry
The effects of N‐acetylcysteine (NAC) on the pharmacokinetic parameters of acetaminophen (AP) in adult female beagles were studied. Each of eight dogs received a single i.v. injection of 150 mg/kg of AP as a 5% solution in a vehicle of 40% aqueous propylene glycol at 0h. Each of four AP‐treated dogs (Group I) received an oral dose of 140 mg/kg NAC as a 20% aqueous solution at 0h, and 70 mg/kg at 30 min and 1h post‐AP administration. Four dogs (Group II) served as controls and received isotonic saline orally. Mild signs of AP toxicosis seen in both groups within 2‐3h of AP administration including depression, weakness, recumbency and methaemoglobinaemia. Relative to Group II, treatment with NAC (Group I) enhanced the elimination of AP from the body as indicated by the decreased plasma half‐life (t 1/2 =1.06h for Group I v. 1.78h for Group II) and a higher elimination rate constant (ß=0.67/h for Group I v. 0.40/h for Group II). Changes in the area under plasma concentration curve data (AUC=0.39 mg.h/ml for Group I v. 0.65 mg.h/ml for Group II) were associated with a 61% increase in total body clearance of AP in Group I. The apparent volume of drug distribution Vd area was not affected.