Abstract
The plasma binding of phenytoin and the relationship between phenytoin concentrations in salivary and plasma ultrafiltrates were evaluated in pediatric epileptic patients aged 2-15 years. Paired samples of plasma and saliva were ultrafiltered through an Amicon YMT membrane. Phenytoin concentrations were measured by a gas-liquid chromatography procedure. The phenytoin free fraction among pediatric epilepsy patients not taking valproic acid was normally distributed with a mean (+/- SD) of 9.2 +/- 1.8%. The mean (+/- SD) free phenytoin fraction among patients also taking valproic acid was 13.2 +/- 4.5%. Salivary ultrafiltrates exhibited a close correspondence with plasma ultrafiltrate concentrations, and the ratio of salivary to plasma ultrafiltrate concentrations was 1.06 +/- 0.15. Substantial intraindividual variation in the phenytoin free fraction and the increase in free fraction among patients on valproic acid emphasize the importance of using plasma unbound levels for monitoring phenytoin. The close agreement between plasma and salivary ultrafiltrate concentrations suggests that the latter will provide a practical noninvasive means of monitoring phenytoin.
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