Increased serum sulfate concentrations in man due to environmental factors: effects on acetaminophen metabolism.
Serum sulfate concentrations were determined in volunteers consuming municipal drinking water with varying sulfate contents--77 ppm in Saskatoon and 1157 ppm in Rosetown. The serum sulfate concentrations were subsequently monitored after the administration of single or multiple-dosing regimens of acetaminophen, which undergoes sulfoconjugation, to determine whether sulfate concentrations in serum changed. Average serum sulfate concentrations were 0.35 mmol/L (Saskatoon) and 0.50 mmol/L (Rosetown). Saskatoon volunteers had a significant fall in serum sulfate concentrations during the multiple-dosing regimen. This was not seen in the Rosetown participants. The rates of urinary excretion and renal clearance of sulfate were significantly higher in the Rosetown volunteers. Except for the multiple-dosing t1/2 levels, the Cmax, tmax, AUC and Cl/f of acetaminophen were not significantly different within or between the 2 groups. The excretion of sulfate and glucuronide conjugates of acetaminophen was not significantly different between the 2 groups, but there was a difference within each group with respect to single and multiple-doses. Excretion of the sulfate conjugate fell significantly in the Saskatoon volunteers during the multiple-dose portion of the study, whereas the percentage excreted as the glucuronide increased. The consumption of 15-fold greater sulfate levels in drinking water increased the sulfate concentration in serum. However, this increased concentration did not significantly alter the sulfoconjugation of acetaminophen.
Hindmarsh
K W
KW
College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
Mayers
D J
DJ
Wallace
S M
SM
Danilkewich
A
A
Ernst
A
A
D000082:Acetaminophen / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001711:Biotransformation; D005260:Female; D006801:Humans; D008297:Male; D013431:Sulfates / Q000032:analysis / Q000097:blood*; D014881:Water Supply / Q000032:analysis*
D013431:Sulfates; D000082:Acetaminophen