Pharmacokinetics of acetaminophen elimination by anephric patients

The pharmacokinetics of acetaminophen elimination were determined in five surgically anephric and five physiologically anephric patients on an interdialysis day, and in three normal adult volunteers. There was no significant difference in the biologic half-life and no apparent difference in the volume of distribution of acetaminophen between the three groups of subjects but the anephrics, unlike the normal subjects, showed pronounced accumulation of acetaminophen glucuronide and sulfate in plasma. The apparent volume of distribution for conjugated acetaminophen is considerably smaller than that for the unmetabolized drug even though neither acetaminophen nor its glucuronide or sulfate is significantly bound to plasma proteins. The results of this study indicate that the kidneys do not contribute significantly to the elimination of acetaminophen in man. Sin ce acetaminophen is eliminated largely by conjugation with glucuronic acid and sulfate, it can be concluded that the kidneys do not contribute significantly to the formation of these metabolites.