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Observational Study
. 2024 Nov;80(11):1751-1759.
doi: 10.1007/s00228-024-03741-2. Epub 2024 Aug 16.

Therapeutic drug monitoring for valproate: deriving a novel formula for calculation of free concentration

Erna Pretorius  1 , Paulina van Zyl  2 , Gina Joubert  3
Affiliations
Observational Study

Therapeutic drug monitoring for valproate: deriving a novel formula for calculation of free concentration

Erna Pretorius et al. Eur J Clin Pharmacol. 2024 Nov.

Abstract

Background: Monitoring free valproate concentrations, as with other highly protein-bound anticonvulsants, is essential in clinical situations where protein binding may be disrupted. Conversion of measured total concentrations to approximate free concentrations offers a cost-effective alternative. This study evaluated the relationship between total and free valproate concentrations for discordance and the impact of key determinants. A novel formula was devised that incorporates significant variables.

Methods: A multicentre, cross-sectional observational analytical study included 101 subjects 18 years and older using valproate for 6 months or longer. Participants were recruited from private and public sector healthcare settings from primary to tertiary level in, South Africa, during 2017-2019.

Results: Free valproate concentrations could be measured for 84 subjects. Discordance for concomitant total and free valproate concentrations was 79.1%. Among 19 participants with elevated free concentrations, 15 (78.9%) had total valproate concentrations within the recommended reference range. Calculations based on the study-derived formula were more accurate in predicting free valproate concentration than previously proposed methods.

Conclusion: This study proposes that the novel formula for calculating free valproate enables more accurate prediction.

Keywords: Calculation; Formula; Free concentration; Therapeutic drug monitoring; Total concentration; Valproate.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Relationship between free valproic acid and total valproic acid concentrations (n = 84). The red trendline presents the polynomial correlation, and the green line presents the linear correlation
Fig. 2
Fig. 2
Scatter plot of the relationship between valproic acid free fraction (%) plotted against total valproic acid concentration (µg/mL). The red trendline represents a polynomial correlation
Fig. 3
Fig. 3
Median albumin (g/L) concentration plotted against age grouped in 10-year intervals (n = 84)
Fig. 4
Fig. 4
Scatter plot of the relationship between the estimated free valproic acid concentration using the new study-derived formula, compared to the measured free valproic acid concentration. The dotted red trendline presents the data according to a linear equation
See this image and copyright information in PMC

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