Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration

Plasma paracetamol concentrations were measured in 6 volunteers after single intravenous (1000 mg) and oral (500 mg, 1000 mg and 2000 mg) doses of the drug. Paracetamol levels declined multiphasically with a mean clearance after intravenous administration of 352 +/- 40 ml/min. A two-compartment open model appeared to describe the decline adequately. Comparison of the areas under the plasma concentration-time curves (AUC) indicated that oral bioavailability increased from 0.63 +/- 0.02 after 500 mg, to 0.89 +/- 0.04 and 0.87 +/- 0.08 after 1000 mg and 2000 mg, respectively. As a consequence of the incomplete bioavailability of paracetamol, as well as its multicompartmental distribution, accurate estimates of its distribution volume and clearance cannot be obtained if the drug is given orally. However, an estimate of its total plasma clearance may be derived from the AUC after a 500 mg oral dose.