Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs

The serum concentration profile of paracetamol has been determined after administration of single 1000 mg intravenous and oral doses in six normal subjects and six epileptic patients on chronic antiepileptic drug therapy. The urinary excretion of free and conjugated paracetamol has also been determined. Following intravenous administration, serum paracetamol concentration declined with first-order kinetics. Both elimination rate and total body clearance were higher in the epileptic patients, although in neither case was the difference statistically significant. The oral bioavailability (mean ± s.e. mean) was significantly lower in the epileptic patients than in the normal subjects (0.77 ± 0.03 and 0.89 ± 0.02 respectively, P <0.01), whereas the urinary excretion total (free + conjugated) paracetamol was almost identical in the two groups. It is suggested that the lower bioavailability of paracetamol in the epileptic patients results from enhancement of first-pass metabolism, secondary to enzyme induction.