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Effects of aspirin on salivary and serum phenytoin kinetics in healthy subjects
Author(s) -
Paxton James W
Publication year - 1980
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1980.26
Subject(s) - phenytoin , aspirin , saliva , chemistry , pharmacokinetics , pharmacology , in vivo , drug , endocrinology , medicine , therapeutic index , biochemistry , biology , microbiology and biotechnology , psychiatry , epilepsy
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 (½β) of total serum DPH but there was a trend toward reduced ½β 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. Clinical Pharmacology and Therapeutics (1980) 27 , 170–178; doi: 10.1038/clpt.1980.26