Monitoring of Sodium Valproate and Its Metabolite 2-Propyl-2-Pentenoic Acid in Blood and Analysis of Factors Influencing Hepatotoxicity
DOI:
https://doi.org/10.56147/jbhs.2.6.94Keywords:
- Sodium valproate,
- 2-propyl-2-pentenoic acid,
- Liver injury,
- Plasma concentration,
- Logistic regression
Abstract
Objective: To investigate factors affecting the attainment of VPA plasma concentration targets in pediatric epilepsy patients and to analyze the relationship between 2-ene-VPA plasma concentration and VPA plasma concentration, dosing regimen, as well as liver and kidney function parameters.
Methods: Based on inclusion and exclusion criteria, retrospective analysis was conducted on pediatric epilepsy patients treated at our hospital. VPA and its metabolite 2-ene-VPA plasma concentrations were measured, along with basic patient information and biochemical indicators such as liver and kidney function. Potential factors influencing VPA plasma concentration attainment were analyzed.
Results and conclusion: (1) Statistically significant differences in VPA plasma concentration were observed among the VPA group, VPA combined with LEV group, VPA combined with TPM group and VPA combined with LTG group (F=17.27, P<0.05). No statistically significant differences were found in 2-ene-VPA plasma concentration (F=0.045, P>0.05); There was no significant difference in VPA blood concentration between the two groups (P>0.05); (2) The dosage and formulation of VPA significantly influenced the achievement of target blood concentration (P<0.05). Logistic regression analysis revealed that the formulation, dosage and concomitant use of Topiramate (TMP) also had statistically significant effects on VPA blood concentration (P<0.05); (3) (1) In the VPA oral solution group, there was a correlation between VPA blood concentration and 2-ene-VPA blood concentration (P=0.035, R=0.176), while no correlation was observed in other groups; (2) The correlation between VPA dosage and blood concentration was low: VPA oral solution group (P<0.001, R=0.483), VPA sustained-release tablet group (P<0.001, R=0.516) and 15-30/(kg·d) dosage group (P<0.001, R=0.305); (3) No correlation was found between VPA dosage and 2-ene-VPA blood concentration; (4) VPA blood concentration showed correlations with Creatinine (CREA) (P<0.001, R=0.269), Total Protein (TP) (P<0.001, R=-0.158) and Globulin (GLB) (P<0.001, R=-0.229).
Conclusion: Sodium valproate exhibits significant individual variations in blood concentration. Dosage and formulation are critical factors affecting VPA blood concentration attainment. Clinical monitoring of blood concentration, Alanine Aminotransferase (ALT) and creatinine levels is essential.
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References
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