Human platelets contain two independently regulated forms of the drug conjugating enzyme, phenol sulfotransferase (PST). One form of platelet PST activity is relatively thermolabile (TL) and the other is relatively thermostable (TS). Acetaminophen is a substrate for both the TS and TL forms of PST. Our aim was to determine whether individual variations in platelet PST activity might reflect variations in the sulfate conjugation of oral acetaminophen. Platelet PST activity was measured in blood samples from 29 randomly selected subjects. There was no significant correlation between the independently regulated activities of the TS and TL forms of PST in the platelets of these subjects (r = 0.16, P > 0.4). Each of the 29 subjects ingested 10 mg/kg acetaminophen and 24-hr urinary excretions of acetaminophen, acetaminophen glucuronide, and acetaminophen sulfate were measured. Average 24-hr urinary excretions of acetaminophen, acetaminophen glucuronide, and acetaminophen sulfate were 2.3%, 46.9%, and 35.0% of the total dose of drug. There were significant correlations between the activities of both the TS and TL forms of platelet PST and the excretion of acetaminophen sulfate expressed as a percentage of the dose of the drug (r = 0.621, P < 0.001; r = 0.456, P < 0.02). The correlation coefficient between the TS activity and the excretion of acetaminophen sulfate was significant when the excretion of sulfate conjugate was expressed as a percentage of the sum of acetaminophen plus conjugated metabolites excreted (r = 0.565, P < 0.002). Our data demonstrate that relative levels of platelet PST activity reflect individual variations in the urinary excretion of the sulfate conjugate of acetaminophen.
ASJC Scopus subject areas
- Pharmacology (medical)