EFFECT OF SALIVA FLOW-RATE ON SALIVA PHENYTOIN CONCENTRATIONS - IMPLICATIONS FOR THERAPEUTIC MONITORING

The effect of atropine-induced reductions in saliva flow rate on saliv a phenytoin concentrations were evaluated in a randomised placebo-cont rolled 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 AUC(0- 4 h) for saliva flow rate was significantly reduced by atropine (245 g vs 327 g) and the saliva phenytoin AUC(0-4 h) was significantly incre ased (5.6 mu g.ml(-1).h vs 4.5 mu g.ml(-1).h) without affecting plasma phenytoin concentrations. The saliva/plasma phenytoin AUC(0-4 h) rati o was therefore significantly increased by atropine (0.15 vs 0.12). Ho wever, there was a poor correlation between saliva/plasma phenytoin co ncentration 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 req uired when saliva phenytoin concentrations are used for therapeutic mo nitoring in the presence of factors which may affect saliva flow rate.