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Should we routinely measure free plasma phenytoin concentration?
British Journal of Clinical Pharmacology
|January 1, 1984
Summary
Routine measurement of free phenytoin levels is unnecessary for most epilepsy patients. Total plasma phenytoin concentration reliably reflects unbound drug levels, simplifying therapeutic drug monitoring.
Area of Science:
- Pharmacokinetics
- Clinical Pharmacy
- Epileptology
Background:
- Phenytoin is a widely used antiepileptic drug.
- Plasma protein binding influences phenytoin's efficacy and toxicity.
- Understanding phenytoin binding variability is crucial for therapeutic drug monitoring.
Purpose of the Study:
- To investigate the variability of phenytoin plasma protein binding in epileptic patients.
- To determine if routine free phenytoin concentration monitoring is necessary.
Main Methods:
- Investigated plasma protein binding of phenytoin in 56 epileptic outpatients.
- Measured free phenytoin fraction using equilibrium dialysis at 37°C.
- Quantified total phenytoin concentration via homogenous enzyme immunoassay.
Main Results:
- Free phenytoin fraction showed low variability (median 0.144, range 0.123-0.177).
- No relationship observed between free fraction and total phenytoin concentration.
- A strong correlation (r=0.986) existed between free and total phenytoin concentrations.
- Patients taking sodium valproate showed a higher median free fraction (0.174).
Conclusions:
- Total plasma phenytoin concentration closely reflects free (unbound) drug levels in most epileptic patients.
- Routine estimation of free phenytoin concentration is generally unnecessary.
- Free phenytoin monitoring is recommended only in specific cases like renal/hepatic disease or adverse effects at low total concentrations.