Salivary secretion of paracetamol in man

Plasma and saliva paracetamol levels were measured by HPLC in ten healthy volunteers who took a therapeutic dose after an overnight fast. Salivary levels of the drug were consistently and significantly higher than those in plasma for the first 50 min after oral ingestion, but saliva and plasma levels correlated closely during the elimination phase. There was a highly significant correlation between the AUC 0-alpha calculated from saliva and plasma paracetamol concentration-time curves. The elevated saliva/plasma ratio for the first 50 min was not due to loss of paracetamol from plasma during sample preparation, binding to plasma protein or adsorption to the buccal mucosa. Administration of probenecid in an attempt to block possible active secretion of paracetamol into saliva did not significantly alter the saliva/plasma concentration ratio for the first 50 min, but did significantly reduce this ratio in the time period 125-360 min. The experimental data conformed to a recently proposed model in which elevated saliva/plasma ratios during the early stages following oral ingestion were related to ongoing absorption into the arterial system.