Abstracts

Rationale: Phenytoin has a narrow therapeutic window. Interpretation of phenytoin serum levels are complicated by the drug’s high degree of protein binding. 10% of the total serum phenytoin measured in the body circulates as the free unbound pharmacologically active drug. In normal healthy adults, monitoring of total serum phenytoin levels suffice. However, due to altered protein binding pharmacokinetics, total serum phenytoin levels do not accurately represent therapeutic phenytoin levels in the elderly, malnourished, and critically ill. Various equations to estimate a corrected total serum phenytoin level in these patients have been developed. The objective of our study was to evaluate phenytoin protein binding, assess the validity of Winter-Tozer and Modified Winter-Tozer equations and develop a modified equation for estimation of corrected total serum phenytoin levels in hospitalized veterans. Methods: This was a retrospective chart review. Patients with documented free and total phenytoin levels taken at VA West Los Angeles Medical Center from 1999 to 2010 were identified. Percent phenytoin protein binding was determined by the following equation: % Bound Phenytoin = 100 - (total phenytoin/free phenytoin). The following equations used to estimate a normalized total serum phenytoin level were evaluated: 1) C(normal) = [C(observed)/(0.1 x albumin + 0.1)]; 2) C(normal) = [C(observed)/(0.2 x albumin + 0.1)]; 3) C(normal) = [C(observed)/(0.25 x albumin + 0.1)]; where C(normal) = a normalized serum phenytoin concentration that would be expected in non-hypoalbuminemic patients and where C(observed) = the observed serum phenytoin concentration in hypoalbuminemic patients and 4) the Modified  Winter-Tozer coefficient= C(observed)/(0.29×albumin)+0.1; where C(observed) = the observed serum phenytoin concentration in critically ill. Results: 1315 sets of free and total phenytoin levels were identified. 719 sets of levels met inclusion criteria. 59% of patients were greater than 60 years of age. 33% of patients were classified as hypoalbuminemic with albumin levels less than 3.2 g/dL. 26% of patients were hospitalized in the intensive care unit (ICU) at the time of phenytoin level collection. The mean percent phenytoin binding in our patient population overall was 87.9%. Further analysis showed decreased phenytoin binding in renally impaired (85%), elderly (87%), hypoalbuminemic (83%), and critically ill (83%). Normal protein binding was observed in patients who were ambulatory with normal albumin levels. All equations did not estimate corrected total phenytoin levels well. Equations 1 and 4 failed to provide estimates of normalized total phenytoin level that were within +/- 2.0 mcg/mL of what was expected based on observed free phenytoin levels.  Conclusions: Phenytoin protein binding is variable depending on the population studied. Common equations used to estimate a normalized total phenytoin total levels are not accurate. A revised and more accurate equation for estimation of normalized total phenytoin levels in hospitalized veterans has been developed and will be presented. Funding: None