Impact of Population-Specific Phenytoin Correction Factors on Estimation of Free Phenytoin Concentrations in a Community Teaching Hospital
Abriana M. Palumbo, Andrew Soliman, Kaysey Cloud, Khang Tran, Saeed K. Alzghari, Margarita TaburyanskayaBackground:
Phenytoin is a highly protein-bound medication and monitored due to its narrow therapeutic range. Free phenytoin serum concentratinos (fPHT m ) are not readily available in many institutions.
Objective:
To evaluate whether population-specific correction factors (CFs) improve estimated free phenytoin serum concentrations (fPHTe) compared with traditional Winter-Tozer CF.
Methods:
This retrospective review included adults with same-day measured total phenytoin serum concentrations (mPHT), fPHT m , albumin, and blood urea nitrogen (BUN) values. Patients were stratified by active/breakthrough seizures, intermittent hemodialysis (IHD), or adults younger than 65. Patient-specific fPHT m percentages were used in the estimation of fPHTe.
Results:
Of 126 phenytoin levels reviewed, 66 met inclusion criteria. Population-specific CFs demonstrated lower bias and greater precision. In patients with active/breakthrough seizures and BUN <50 mg/dL, CF 0.29 improved accuracy compared with CF 0.2 (reduced mean percentage error [MPE] −59.59 vs −111.99 – indicating overprediction, root mean square error [RMSE] 1.79 vs 2.91), with similar trends when BUN exceeded 50 g/dL. A preliminary finding among adult patients younger than 65 showed better performance with a CF 0.275 than CF 0.2, with lower MPE (−40.43 vs −78.98) and RMSE (1.32 vs 2.16). In the IHD cohort, CF 0.201 outperformed CF 0.1 (MPE −74.40 vs −197.53 and RMSE 2.07 vs 5.32).
Conclusion and Relevance:
Population-specific CF estimated fPHT e more accurately and precisely than traditional CF. Findings remain preliminary due to limited representation, and further research is needed to improve CF selection across various subgroups.