Elimination of phenytoin in toxic overdose

Phenytoin is widely used for the management of seizures. Fortunately overdosage with this drug is rare. We performed a prospective study to investigate the elimination kinetics of phenytoin in toxic overdose. All patients were only on phenytoin and not on other anticonvulsants. Phenytoin toxicity was defined by clinical features and correlated with drug levels. Daily phenytoin levels were obtained until they were less than or equal to 15 mcg/ml. Nine patients with age ranging from 20 to 66-years-old were recruited. Sex ratio was male:female, 5:4. Initial phenytoin levels ranged from 34 to 57.5 mcg/ml. Serum phenytoin levels of three patients remained relatively constant for 2-5 days before declining in a steady fashion. Phenytoin levels of the remaining patients declined in an almost linear manner. Regression analysis of all patients showed that the slope terms were highly significant (with low P-values) and corresponding R(2) values were close to 1. Different patients have different rates of metabolism; in seven of nine patients, levels declined between 4.6 and 5.9 mcg/ml per day. Knowledge of the rate of elimination assists the clinician in deciding on the best time to reinstitute phenytoin therapy.