Effects of aspirin on salivary and serum phenytoin kinetics in healthy subjects.

In vitro studies have shown that phenytoin (DPH) is displaced from plasma protein binding sites by some drugs. These results have been extrapolated to suggest that, in vivo, this may cause a rise in the free concentration, leading to a greater pharmacologic effect. We examined the effects of aspirin on the levels and kinetics of total serum DPH and free drug as represented by salivary concentrations in 7 healthy subjects. Aspirin induced a decrease (mean, 27.4 +/- 3.7%) in total serum DPH concentration but no corresponding change in salivary concentration. During continued aspirin administration, no change was observed in elimination half-life (t 1/2 beta) of total serum DPH but there was a trend toward reduced t 1/2 beta in saliva. The ratio of saliva to total serum DPH concentration also increased during this period. These results suggest that displacement of DPH from plasma protein binding sites does not result in an increase in free concentration and thus increased pharmacologic activity, but any previous relationship between total serum concentration and therapeutic effect will no longer hold, as a greater proportion of the total concentration will be in the free form and therapeutically active.