Clinical evaluation of plasma free phenytoin measurement and factors influencing its protein binding

The relationship between free phenytoin concentrations and clinical responses, and the factors influencing protein binding of phenytoin were investigated. A total of 119 plasma samples from 70 patients treated orally with phenytoin were analysed. The mean free phenytoin concentration was significantly higher in the patients who received phenytoin monotherapy and were classified as having a complete response (1.25 +/- 1.09 microg/ml) than that in the partial response group (0.59 +/- 0.07 microg/ml), whereas the mean total concentrations were not significantly different between the two groups. Samples were divided into three groups based on the free fraction of phenytoin, i.e. low, <5%; medium, 5%-10%; high, > 10%. The mean age (55.3 +/- 10.9 years) was significantly higher in the high group than in the low (42.7 +/- 21.2 years) and medium (42.8 +/- 16.0 years) groups. The mean creatinine clearance (CLcr) (55.3 +/- 10.9 ml/min) and serum albumin concentration (3.30 +/- 1.25 g/dl) were significantly lower in the high group than the low (88.3 +/- 29.0 ml/min and 4.08 +/- 0.50 g/dl, respectively) and medium (95.0 +/- 32.8 ml/min and 3.95 +/- 0.92 g/dl, respectively) groups. These results suggest that the free phenytoin concentration, rather than the total concentration, is more useful for monitoring antiepileptic effects in patients receiving phenytoin monotherapy. It was also found that the free phenytoin fraction was significantly influenced by aging, CLcr and serum albumin levels.