Differences between the measured and calculated free serum phenytoin concentrations in epileptic patients

Yonsei Med J. 2009 Aug 31;50(4):517-20. doi: 10.3349/ymj.2009.50.4.517. Epub 2009 Aug 19.


Purpose: The pharmacokinetics of phenytoin is complicated by genetic and environmental differences. It is, therefore, important to monitor the serum concentrations in patients who receive phenytoin. Because most of the phenytoin in serum is bound to proteins, the level of serum albumin influences the amount of free phenytoin.

Materials and methods: We compared the measured and calculated free phenytoin levels in epileptic patients who were taking phenytoin monotherapy, using the Sheiner-Tozer equation. A total of 49 patients (30 men and 19 women; age range, 15 - 87 years) were included in the study and their trough serum phenytoin and albumin concentrations were analyzed.

Results: The linear correlation between free and total phenytoin concentrations was moderate (r = 0.822, p < 0.001). The mean difference between measured and calculated free phenytoin was large (0.65 +/- 0.88 microg/mL; 95% confidence interval (CI), -1.11 to 2.41). After dividing the patients into groups by albumin concentration, hypoalbuminemic patients (< 3.5 g/dL) more often had a greater percent difference (> or = 20%) than observed in the normoalbuminemic (> or = 3.5 g/dL) group.

Conclusion: In hypoalbuminemic patients, the measurement of free phenytoin level is necessary to properly evaluate the phenytoin level than that calculated from total phenytoin level.

Keywords: Phenytoin; epilepsy; hypoalbuminemia.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / blood*
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / therapeutic use
  • Epilepsy / blood*
  • Epilepsy / drug therapy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenytoin / blood*
  • Phenytoin / pharmacokinetics
  • Phenytoin / therapeutic use
  • Young Adult


  • Anticonvulsants
  • Phenytoin