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

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Abstract
In vitro studies showed that phenytoin (DPH) is displaced from plasma protein binding sites by some drugs. The results were extrapolated to suggest that, in vivo, this may cause a rise in the free concentration, leading to a greater pharmacologic effect. The effects of aspirin on the levels and kinetics of total serum DPH and free drug as represented by salivary concentrations in 7 healthy [human] subjects was studied. 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 seen in elimination half-life (t1/2.beta.) of total serum DPH but there was a trend toward reduced t1/2.beta. in saliva. The ratio of saliva to total serum DPH concentration increased during this period. Apparently displacement of DPH from plasma protein binding sites does not cause an increase in free concentration and thus increased pharmacologic activity; 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.