(681) Impact of Adjusted Valproic Acid Levels in Hypoalbuminemia: Single-Center Cohort Study

Introduction: Valproic acid (VPA) binds up to 90% to serum proteins, mainly albumin, affecting drug clearance in hypoalbuminemia. Data on patient outcomes for adjusted VPA levels in hypoalbuminemia are limited. This study aims to compare the effectiveness and adverse effects of adjusted vs. total VPA levels in hypoalbuminemia patients.

Methods: This single-center retrospective cohort study analyzed adult patients with therapeutic total valproic acid levels and albumin measured within 48 hours of administration, from January 1, 2016, to December 31, 2022. Total and adjusted valproic acid levels were compared using ROC curves and AUCs by the DeLong method. Safety endpoints included hepatotoxicity, hyperammonemia, hyponatremia, and thrombocytopenia. Effectiveness endpoints included seizure prediction, status epilepticus, and the need for additional antiepileptic medications during hospitalization.

Results: Out of 1622 screened patients, 71 with hypoalbuminemia received VPA. The ROC analysis results showed that the threshold of aVPAc (154.19 mg/dL) had higher sensitivity (86% vs. 71%) and lower specificity (47% vs. 72%) compared to the tVPA at a threshold of (67.53 mg/dL) in predicting hepatotoxicity with (ROC-AUC 0.64 [CI: 0.41 - 0.86; p= 0.51]; however, the outcome was not statistically significant. Additionally, Five patients representing (23%) had significant hyper-ammonia during their admission with aVPAc at a threshold level of 188.00 mg/dL, they exhibited higher sensitivity (100% vs. 40%) and lower specificity (82% vs. 88 %) in predicting hyperammonemia compared to the tVPA with a threshold of (74.32 mg/dL) (ROC-AUC 0.95 Moreover, (55%) of patients receiving valproic acid required additional anti-seizure, at aVPAc threshold (131.54 mg/dL) compared to the tVPAc at level (60.32 mg/dL), aVPAc  shown lower sensitivity  (44% vs. 64% ) and higher specificity (84% vs. 72%) with (ROC-AUC 0.69 [CI: 0.57 - 0.82; p= 0.04].

Conclusions: Adjusted Valproic acid concentrations (aVPAc) predict hepatotoxicity and hyperammonemia better than total levels (tVPAc). This suggests aVPAc can improve safety in hypoalbuminemic patients. Larger randomized trials are needed to confirm these findings.