OBJECTIVE: To assess the reliability of salivary phenytoin (PHT) concentrations and predicted free PHT levels by Sheiner-Tozer equation in order to substitute measured free PHT concentrations in critically ill patients. METHODOLOGY: Twenty-four neurocritically ill adult patients receiving intravenous PHT were included in the study. Analyses of total, free plasma and saliva PHT concentrations were performed by fluorescence polarization immunoassay. Plasma albumin levels were also determined. RESULTS: Free PHT concentrations as well as salivary levels better correlate to clinical effect than total drug concentrations. Linear regression analysis showed a strong correlation between estimated free PHT concentrations by Sheiner-Tozer and measured free PHT levels (r=0.835; p<0.001) and salivary PHT concentrations and measured free PHT concentrations (r=0.964; p<0.001). Sheiner-Tozer equation could be misleading in the presence of displacing drugs. CONCLUSIONS: Saliva may serve as a feasible fluid to plasma in order to be used as a surrogate for free concentration monitoring of PHT in this population.
Phenytoin; unbound concentration; saliva concentration; Sheiner-Tozer equation
