Temporal variations in paracetamol absorption and metabolism in man.

When paracetamol (1.5 g) was administered orally to non-fasted healthy subjects, statistically significantly more paracetamol glucuronide was detected in 0-4 h urine when the drug was given at 8.00 a.m. as compared to other times of the day. Compared to administration at 8.00 pm, the urine contained almost twice as much glucuronide. However, there was apparently no temporal variation in the excretion of intact drug and its other metabolites. Marked differences were observed in salivary concentrations of paracetamol during the first 90 min following oral administration at 8.00 a.m. and 8.00 p.m. These data were consistent with a decreased rate of absorption of paracetamol at 8.00 p.m. Paracetamol clearance, elimination half-life and volume of distribution did not differ when the drug was administered by intravenous infusion at 8.00 a.m. and 8.00 p.m. There was also no change in the amounts of paracetamol and metabolites excreted in the urine. There appears to be a temporal variation in the elimination of paracetamol glucuronide following oral administration of paracetamol, which is probably related to a variation in absorption.