Comparison of four valproic acid free fraction determination methods used in clinical practice

Abstract

ObjectiveGiven that hypoalbuminemia tends to result in higher free fraction concentrations of valproic acid, different methods have been developed to determine the latter in patients with this condition. The aim of this study is to assess the reliability of these methods and, if necessary, design a new estimation method. MethodA retrospective analysis was carried out by the Pharmacy Department of Severo Ochoa University Hospital of admitted patients with at least one trough concentration of valproic acid between October 2017 and February 2019. The estimation methods used were those developed by Kodama, Hermida, Doré, as well as a new method proposed in the study. A total of 17 serum valproic acid concentrations were used to determine the free fraction of valproic acid with each method; the values obtained were compared with the results obtained following laboratory determinations. Accuracy and precision were calculated using mean error and root mean square error, respectively. ResultsThe comparison between observed and predicted free valproic acid values using the methods under investigation showed that the method proposed in this study provides the highest reliability as it presents the highest accuracy and precision. The worst results were those obtained using the Kodama method, which does not consider albuminemia, an essential variable that determines the concentration, therapeutic effect and toxicity of valproic acid. ConclusionsGiven that the method proposed in this study proved to be superior to the other methods analyzed, we believe it can be reliably used to estimate free valproic acid levels in patients with hypoalbuminemia.