Fluctuations in steady-state phenytoin concentrations as measured in saliva in children.

Data from two studies are reported. In the first, salivary concentrations were monitored hourly in epileptic children receiving phenytoin monotherapy, twice daily. The results indicated rapid drug absorption in the majority with time of maximum concentration occurring most frequently 1-5 hours following morning medication. A number of children showed moderate to large fluctuations in steady-state drug concentrations during the day, and there was a mean peak-to-trough fluctuation of 52% over the group. In the second study, drug concentration data are reported from an ongoing investigation of phenytoin's behavioral effects. Medication was given before sampling on one day, whereas it was delayed until after sample collection on the alternate day. Results indicated that salivary concentrations were higher, for 38 of 41 subjects, on the expected-high day with an overall mean difference in drug concentration of 56% between the 2 days. These findings were discussed in terms of their implications for clinical management and the possible relation of drug concentrations to psychomotor function.