Interpatient and intrapatient variability in phenytoin protein binding

Area of Science:

• Pharmacology
• Clinical Chemistry
• Internal Medicine

Background:

• Phenytoin is an anticonvulsant medication with a narrow therapeutic index.
• Accurate therapeutic drug monitoring (TDM) of phenytoin is crucial for efficacy and safety.
• Phenytoin protein binding can be influenced by various factors, leading to variability in free concentrations.

Purpose of the Study:

• To assess the relationship between total and free phenytoin serum concentrations and serum albumin levels.
• To evaluate the reliability of estimating free phenytoin from total phenytoin concentrations in hospitalized patients.
• To determine the interpatient and intrapatient variability of the phenytoin free fraction.

Main Methods:

• Retrospective analysis of paired serum samples from 48 hospitalized patients.
• Measurement of total and free phenytoin serum concentrations and serum albumin.
• Calculation of phenytoin free fraction and albumin-adjusted total phenytoin concentrations.
• Recording of concomitant medications.

Main Results:

• Mean phenytoin free fraction was 15% ± 7%, with significant interpatient (65%) and intrapatient (85%) variability.
• Correction for serum albumin did not improve the estimation of free phenytoin concentrations.
• Strong overall correlation between total and free phenytoin concentrations existed, but with excessive variability in protein binding.

Conclusions:

• Total phenytoin serum concentrations are unreliable for monitoring in hospitalized patients due to high variability.
• Free phenytoin serum concentrations should be considered for monitoring to ensure therapeutic efficacy and patient safety.
• Individualized monitoring strategies are necessary given the unpredictable protein binding of phenytoin.