Data point weighting in pharmacokinetic analysis: intravenous paracetamol in man

Compartmental analysis of plasma paracetamol concentrations following intravenous injection of 12 mg kg-1 in aqueous solution to normal subjects was performed using analogue and digital computer methods. Using a "simplex" non-linear optimization procedure, the pharmacokinetic parameters were found to be influenced considerably by the choice of the weighting factors (W1) attributed to individual data points. The plasma half-life of paracetamol varied by up to a seven-fold with the weighting factors selected. However, the predicted mean steady-state plasma concentrations were shown to be relatively little affected by the different weighting factors.