Depletion of endogenous inorganic sulfate can have pronounced effects on the elimination kinetics and metabolic fate of phenolic drugs. Our purpose was to determine the effects of acetaminophen (which is partly metabolized to acetaminophen sulfate), ascorbic acid (subject to more limited sulfation than acetaminophen), and sodium sulfate (useful for sulfate repletion by the oral route) on the serum concentration and renal excretion of inorganic sulfate in healthy adults. Six men and two women, 26 to 35 yr old, were studied on four occasions that were at least 4 days apart. They received no medication, 1.5 gm acetaminophen, 6 gm ascorbic acid, or 9 gm sodium sulfate decahydrate orally, in aqueous solution. A blood sample was obtained 2 hr later and urine was collected from 1 to 3 hr. Serum inorganic sulfate concentrations (mean ± SD), 0.410 ± 0.043 mM in the control period, were decreased after acetaminophen (0.311 ± 0.043 mM, P < 0.001), increased after sodium sulfate (0.513 ± 0.055 mM, P < 0.001), and apparently unchanged after ascorbic acid (0.417 ± 0.059 mM). The urinary excretion of inorganic sulfate was decreased after acetaminophen and increased after sodium sulfate. The renal clearance of endogenous creatinine was not affected by any of the treatments. The renal tubular reabsorption of inorganic sulfate is capacity limited, as evidenced by the decrease of the reabsorbed fraction with increasing glomerular filtration rate of the anion (r = − 0.54, P < 0.005). This saturable reabsorption facilitates sulfate homeostasis.

Clinical Pharmacology and Therapeutics (1983) 33, 529–536; doi:10.1038/clpt.1983.72