Yonsei Med J.  2009 Aug;50(4):517-520. 10.3349/ymj.2009.50.4.517.

Differences between the Measured and Calculated Free Serum Phenytoin Concentrations in Epileptic Patients

• Hong JM
• Choi YC
• Kim WJ

• KMID: 1758610
• DOI: http://doi.org/10.3349/ymj.2009.50.4.517

Abstract

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.

Keyword

Phenytoin; epilepsy; hypoalbuminemia

MeSH Terms

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

Figure

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  Fig. 1 Distribution of free and total serum phenytoin concentrations.

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  Fig. 2 The mean difference (solid line) between actual and calculated free phenytoin. One tenth of the Sheiner-Tozer corrected value was 0.65 ± 0.88 µg/mL; 95% confidence interval, -1.11 to 2.41, and considerable scatter is observed in this relationship.

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  Fig. 3 Phenytoin binding ratio and serum albumin concentration in patients. The binding ratio of free to total phenytoin is greater (25.3% free phenytoin) in patients with hypoalbuminemia (less than 3.5 g/dL) (p = 0.002).

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