Comparison of free fraction serum valproic acid concentrations between inpatients and outpatients

Abstract

The median free fraction of valproic acid was significantly higher in inpatients than in outpatients. Low albumin concentration was a predictor of discordance between free and total valproic acid concentrations.

Clinical Importance of Monitoring Unbound Valproic Acid Concentration in Patients with Hypoalbuminemia

“…Indeed, as confirmed in this study, the binding of VPA to albumin was the major determinant of the unbound VPA concentration. Our results are consistent with those previously published . The latter study showed that low albumin level was the unique independent risk factor for therapeutic discordance between total and unbound VPA concentration by multivariable logistic regression .…”

“…Our results are consistent with those previously published . The latter study showed that low albumin level was the unique independent risk factor for therapeutic discordance between total and unbound VPA concentration by multivariable logistic regression . However, hypertriglyceridemia, hyperbilirubinemia, chronic renal failure, hepatic dysfunction, and certain drug interactions are also known to influence the protein binding of VPA .…”

“…There is significant interindividual variability in VPA blood concentrations . Several studies illustrated that VPA's clinical pharmacokinetic evaluation based on total drug concentration may be misleading as a result of reduced protein binding, saturable protein binding, and saturable metabolism . Unbound VPA clearance decreases with increasing VPA serum concentration, particularly in the elderly .…”

Valproate Protein Binding Is Highly Variable in ICU Patients and Not Predicted by Total Serum Concentrations: A Case Series and Literature Review

“…30,31 Hypoalbuminemia is a common risk factor for an increased free fraction of valproate. 4,6,32,33 The largest study published to date (including both hospitalized and outpatients) concluded that albumin values less than 3.5 g/L were associated with increased valproate free fractions, the only factor explaining therapeutic discordance between free and total serum valproate concentrations. 33 All patients in our study had albumin concentrations less than 3.7 g/dl.…”

“…4,6,32,33 The largest study published to date (including both hospitalized and outpatients) concluded that albumin values less than 3.5 g/L were associated with increased valproate free fractions, the only factor explaining therapeutic discordance between free and total serum valproate concentrations. 33 All patients in our study had albumin concentrations less than 3.7 g/dl. Uremia may also alter valproate protein binding, with free fractions of 20% with renal dysfunction compared with 8% without, and a moderate correlation has been observed between valproate free fraction and both serum creatinine and blood urea nitrogen.…”