Acetaminophen elimination half-life in humans is unaffected by short-term consumption of sulfur amino acid-free diet.

Abstract

Sulfation and glutathione (GSH) conjugation are important pathways for elimination of acetaminophen (APAP). Previous studies in rodents show that limitation of dietary sulfur amino acids (SAAs) reduces biosynthesis of 3'-phosphoadenosine-5'-phosphosulfate, the precursor for sulfation, and GSH, the precursor for the mercapturatic acid pathway. The amount of SAA needed for the metabolism of two doses of APAP is equivalent to 62% of the recommended dietary allowance (RDA) for SAA in humans. A decrease in the activity of these metabolic pathways could lead to decreased elimination of the reactive metabolite of APAP and possibly affect risk of APAP use. To determine whether intake of a SAA-deficient diet alters APAP metabolism, a pilot clinical study with a double-blind, cross-over design was performed. Subjects received the RDA for SAA for 3 days for equilibration. After admission to the clinical research unit, subjects were given a chemically defined diet with 100 or 0% of the RDA for SAA for 2 days. On day 3, two doses of APAP (15 mg/kg) or placebo were given successively within a 6-h interval. Plasma samples were collected at baseline and hourly for 12 h, and two 6-h urine aliquots were collected during this time course. The data show that SAA limitation 1) did not change the pattern of APAP metabolites in plasma or urine and 2) did not alter APAP pharmacokinetics. Thus, the results show that 2 days of diet completely devoid of SAA have no effect on APAP metabolism or disposition in healthy humans.