REVISED WINTER-TOZER EQUATION FOR NORMALIZED PHENYTOIN CONCENTRATIONSIN TRAUMA AND ELDERLY PATIENTS WITH HYPOALBUMINEMIA

OBJECTIVE: TO develop a revised equation reflecting the current practi ce of measuring unbound phenytoin at room temperature, and to evaluate the revised Winter-Tozer method of predicting normalized total phenyt oin concentrations in two groups of patients with hypoalbuminemia - el derly nursing home patients and critically ill head trauma patients. D ESIGN: Albumin, unbound phenytoin, and total phenytoin concentrations were obtained from two sources: prospectively from a group of elderly nursing home patients and by a retrospective chart review of trauma pa tients enrolled in a previous double-blind, placebo-controlled study. SETTING: Community nursing homes; a university-affiliated urban teachi ng hospital. PARTICIPANTS: Elderly nursing home patients (n = 46) taki ng chronic phenytoin therapy and patients enrolled in a double-blind, placebo-controlled study (n = 58) evaluating the use of phenytoin to p revent posttraumatic seizures. MAIN OUTCOME MEASURES: Prediction error analysis was performed by using the methods proposed by Sheiner and B eal. Bias and precision were evaluated by calculating the mean predict ion error (MPE) and root mean squared error (RMSE), respectively. RESU LTS: The Winter-Tozer equation consistently overpredicted the normaliz ed phenytoin concentration in the elderly nursing home population (MPE = 3.2, RMSE = 5.9) and the trauma patients (MPE = 3.3, RMSE = 4.8), T he equation was revised to reflect the increased protein binding of ph enytoin with decreased temperature and resulted in significantly decre ased bias in both groups of patients. CONCLUSIONS: The revised equatio n is useful in predicting normalized phenytoin concentrations in both elderly nursing home patients and critically ill trauma patients.