Evidence-based implementation of free phenytoin therapeutic drug monitoring.
BACKGROUND
The majority of laboratories measure total phenytoin concentration for therapeutic drug monitoring. However, there are substantial interindividual variations in free phenytoin concentrations, the pharmacologically active component.


METHODS
We describe the process and data used to implement monitoring of free phenytoin only in an urban medical center. Over a 6-week period, total and free phenytoin concentrations were measured, clinical charts reviewed, and indications for alterations in the percentage of free phenytoin fraction were determined.


RESULTS
Of the 189 phenytoin requests from 139 patients, 136 data points were analyzed. Free phenytoin concentrations were 6.8-35.3%, with 50% outside the expected range of 8-12%. Clinical indications likely responsible for variations were hypoalbuminemia, drug interactions, uremia, pregnancy, and age. Overall, 30% of patients demonstrated a discrepancy between therapeutic, subtherapeutic, or supratherapeutic concentrations between free and total phenytoin concentrations. The largest discordance (53%) occurred in the patient group with free phenytoin <8% or >12%.


CONCLUSIONS
This study supports previous clinical findings that monitoring total phenytoin is not as reliable as free phenytoin as a clinical indicator for therapeutic and nontherapeutic concentrations. Thus, we recommend that therapeutic monitoring should use free phenytoin concentrations only.
Departments of Laboratory Medicine and Pathology and Neurology, Hennepin County Medical Center, University of Minnesota School of Medicine, Minneapolis, MN 55415, USA.
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Burt
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Anderson
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Kloss
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Apple
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000097:blood* / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism*; D002648:Child; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010672:Phenytoin / Q000097:blood* / Q000378:metabolism; D011247:Pregnancy; D011485:Protein Binding
D000927:Anticonvulsants; D001798:Blood Proteins; D010672:Phenytoin