Circadian rhythm of serum sulfate levels in man and acetaminophen pharmacokinetics

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Abstract
Summary The circadian variation of serum inorganic sulfate levels was studied in healthy volunteers. The effect of subchronic acetaminophen administration (650 mg q.i.d. for 4 days) on serum inorganic sulfate levels was investigated and the possible role of fluctuating serum inorganic sulfate levels on the pharmacokinetics of acetaminophen was evaluated. During a 24 h cycle, serum inorganic sulfate levels were lowest in the morning (11.00 h) and typically increased in the afternoon to reach a maximum in the early evening (19.00 h). Average 24 h serum concentrations were 360 μM and the difference between minimum and maximum levels was on average 25.8%. Subchronic administration of acetaminophen (650 mg q.i.d. for 4 days) significantly reduced serum inorganic sulfate levels to a 24 h average of 253 μM. The circadian rhythm, however, was not affected and the difference between minimum (12.00 h) and maximum (18.50 h) serum concentrations was 31.3%. Subchronic acetaminophen administration lead to a significant decrease in the renal excretion (−51%) and renal clearance (−33%) of inorganic sulfate. No significant differences were found in the disposition kinetics of acetaminophen and its glucuronide and sulfate conjugates during two consecutive dosing intervals (08.00–14.00 h, 14.00–20.00 h) on Day 4 of the acetaminophen regimen.