Abstract
The renal clearances of acetaminophen, acetaminophen glucuronide, and acetaminophen sulfate were determined in eight healthy adults 2h after administration of 1.5g of acetaminophen. The renal clearance ratios (relative to creatinine) were 0.058 ± 0.026, 0.890 ± 0.153, and 1.43 ± 0.250 (mean ± SD), respectively. The renal clearance of acetaminophen increased with increasing urine flow rate, and that of acetaminophen sulfate decreased with increasing serum concentration of the conjugate. A strong positive correlation was found between the renal clearances of acetaminophen glucuronide and acetaminophen sulfate, possibly due to blood perfusion rate-dependent renal tubular secretion of the two conjugates. The serum protein binding of acetaminophen (≈20%) and acetaminophen glucuronide (<10%) are minor. Acetaminophen sulfate is >50% protein bound, as determined by equilibrium dialysis and ultrafiltration. The results of these studies are (a) consistent with previous reports of animal studies, indicating that renal excretion of acetaminophen involves glomerular filtration and passive reabsorption and that acetaminophen sulfate is subject to active renal tubular secretion, and (b) compatible with the reported occurrence of renal tubular secretion of acetaminophen glucuronide in animals.
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