Interpatient and intrapatient variability in phenytoin protein binding

The authors retrospectively assessed the relation between total and free serum concentrations and serum albumin in a sample of hospitalized patients to evaluate how well free serum concentrations can be estimated from total phenytoin serum concentrations. The authors also assessed the interpatient and intrapatient variability of the phenytoin free fraction. Paired serum samples of total and free phenytoin serum concentrations and serum albumin were obtained from 48 hospitalized patients (28 males, 20 females; mean age, 51 y; range, 13-90 y). Concomitant medications were recorded. Phenytoin free fraction and adjusted total phenytoin serum concentrations (adjusted for serum albumin) were calculated. One hundred sixty-three samples were obtained (mean, 3.4 samples per patient; range, 1-16 samples); 28 patients had more than one pair of samples obtained. Mean phenytoin free fraction was 15% +/- 7% (range, 4%-61%) for the 163 samples. The variability for the total, free, and free fractions were 65%, 75.9%, and 45.8%, respectively. There was significant variability in the phenytoin free fraction within individual patients who had more than one pair of serum concentrations obtained. The intraindividual coefficient of variation in phenytoin free fraction was 85% +/- 21.3% (range, 2%-94%). Despite strong overall correlation between the total phenytoin serum and free serum concentrations, there is excessive variability in phenytoin protein binding. Correction for serum albumin was not useful in this patient group. Because of significant interpatient and intrapatient variability in phenytoin serum concentrations, monitoring of total serum concentrations is unreliable and free phenytoin serum concentrations should be considered for monitoring in hospitalized patients.