Effect of saliva flow rate on saliva phenytoin concentrations: implications for therapeutic monitoring.

The effect of atropine-induced reductions in saliva flow rate on saliva phenytoin concentrations were evaluated in a randomised placebo-controlled crossover study in a group of epileptic patients stabilised on the drug. Pretreatment with atropine caused significant reductions in saliva flow rates during the first 4 h, compared to saline. The AUC0-4 h for saliva flow rate was significantly reduced by atropine (245 g vs 327 g) and the saliva phenytoin AUC0-4 h was significantly increased (5.6 micrograms.ml-1.h vs 4.5 micrograms.ml-1.h) without affecting plasma phenytoin concentrations. The saliva/plasma phenytoin AUC0-4 h ratio was therefore significantly increased by atropine (0.15 vs 0.12). However, there was a poor correlation between saliva/plasma phenytoin concentration ratios and saliva flow rates for the two treatments in the individual patients (correlation coefficient ranged from 0.25 to 0.65). These findings demonstrate that saliva phenytoin concentrations are increased by reductions in saliva flow rate. Caution is therefore required when saliva phenytoin concentrations are used for therapeutic monitoring in the presence of factors which may affect saliva flow rate.