Purpose
The purpose of this study was to explore appropriate parameters for predicting the free fraction of valproic acid (VPA) and the unbound VPA concentration in patients.
Methods
Datasets from patients treated with VPA were retrospectively evaluated. We analyzed the associations between various parameters and the free fraction of VPA. The Pearson’s correlation coefficient (r) was analyzed by testing for no correlation.
Results
A total of 136 datasets from 75 patients were analyzed in this study. The free fraction of VPA was 0.18 ± 0.07 (range, 0.07–0.46). The parameter that combines total VPA concentration (CtVPA) and serum albumin (SA), (CtVPA [µM] – 2 × SA [µM]), significantly related to the free fraction of VPA (r = 0.76, p < 0.001). This combined parameter-based prediction formula for unbound VPA concentration was constructed. Analysis using previously reported external datasets from patients without severe renal failure showed that the combined parameter also significantly related to the free fraction of VPA (r = 0.72, p < 0.001). Furthermore, the prediction errors of the unbound VPA concentration by the combined parameter-based prediction formula were lower than those of previously reported prediction formulae.
Conclusions
This study indicates that (CtVPA [µM] – 2 × SA [µM]) significantly relates to the free fraction of VPA in patients. This combined parameter may make it possible to predict more accurately the free fraction of VPA and the unbound VPA concentration in patients without severe renal failure than the previously reported formulae.
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