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Accuracy of two equations in determining normalized phenytoin concentrations
L S Mauro1, V F Mauro, K A Bachmann
1Department of Pharmacy Practice, College of Pharmacy, University of Toledo, OH 43606.
DICP : the Annals of Pharmacotherapy
|January 1, 1989
Summary
Two equations for normalizing phenytoin levels in patients with renal failure or hypoalbuminemia were inaccurate. These equations should not be used clinically due to significant over- or underprediction of drug concentrations.
Area of Science:
- Pharmacokinetics
- Clinical Chemistry
Background:
- Accurate therapeutic drug monitoring of phenytoin is crucial for patient safety.
- Renal failure and hypoalbuminemia can significantly alter phenytoin pharmacokinetics, affecting total drug concentrations.
- Existing normalization equations aim to estimate phenytoin levels but their accuracy in specific patient populations requires validation.
Purpose of the Study:
- To evaluate the accuracy of two common equations in normalizing total phenytoin concentrations.
- To assess the reliability of these equations in patients with renal failure and hypoalbuminemia.
Main Methods:
- A prospective study involving 11 renal failure patients and 23 hypoalbuminemic patients receiving phenytoin.
- Assay of free and total phenytoin concentrations in blood samples.
- Statistical comparison (Student's t-test) of normalized phenytoin concentrations derived from equations versus those based on free drug concentration.
Main Results:
- The hypoalbuminemia equation significantly underpredicted normalized phenytoin concentrations (15.7 vs. 19.9 mg/L, p<0.001).
- In renal failure patients, one equation showed acceptable mean values but resulted in over- or underprediction by at least 25% in 5 of 11 patients.
- Significant discrepancies were observed, indicating poor performance of the tested equations in these patient groups.
Conclusions:
- Neither of the evaluated equations accurately normalizes total phenytoin concentrations in patients with renal failure or hypoalbuminemia.
- Clinical use of these equations for phenytoin concentration normalization in these specific patient populations is not recommended.
- Further research is needed to develop and validate reliable methods for phenytoin level normalization in complex patient cases.
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