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The role of sulphate conjugation in the metabolism and disposition of oral and intravenous paracetamol in man.
Author(s) -
Clements JA,
Critchley JA,
Prescott LF
Publication year - 1984
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1984.tb02495.x
Subject(s) - glucuronide , chemistry , pharmacokinetics , conjugate , oral administration , pharmacology , acetaminophen , metabolism , bioavailability , excretion , glucuronidation , enterohepatic circulation , urinary system , medicine , biochemistry , mathematical analysis , mathematics , enzyme , microsome
The effects of paracetamol dose (5 and 20 mg/kg) and route of administration (intravenous and oral) on the urinary excretion of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates were studied in five healthy subjects. The fractional urinary excretion of unchanged paracetamol and its conjugates was independent of the route of administration at both dose levels, suggesting that the gastrointestinal tract is not an important site for paracetamol metabolism. The percentage of the dose excreted as the sulphate conjugate was significantly higher after 5 than after 20 mg/kg (37.7% and 33.3% respectively) and this is consistent with saturation of sulphate conjugation. No significant effect of paracetamol dose upon the area under the plasma concentration‐time curve (AUC), corrected for dose, was found for the sulphate or glucuronide conjugates. The total plasma clearance of paracetamol and the renal clearance of the sulphate conjugate were significantly higher after the 5 than the 20 mg/kg dose (331 +/‐ 42 ml/min and 295 +/‐ 48 ml/min; 273 +/‐ 74 ml/min and 205 +/‐ 46 ml/min respectively). The oral systemic availability of paracetamol was 80% and independent of dose.