Association of valproic acid and 2-propyl-4-pentenoic acid concentrations with adverse reaction in 254 Chinese patients with epilepsy

Abstract

To investigate the correlation of the concentrations of valproic acid (VPA) and 2-propyl-4-pentenoic acid (4-ene-VPA) with their adverse reactions, and to guide the clinical safety and rational use of VPA. Methods: We collected 254 epilepsy outpatients who took long-term use of sodium valproate oral solution single or combined with other antiepileptic drugs from Xiangya Hospital. The plasma concentrations of VPA and 4-ene-VPA in patients were determined by gas chromatography-mass spectrometry (GC-MS). The double variable correlation analysis was performed to analyze the effect of plasma 4-ene-VPA and VPA concentrations on adverse reactions. Results: The correlations between the PLT level and the dosage of VPA (P<0.01 and P<0.05, respectively), and the RBC level and the concentration of VPA (All P<0.01) were significant negatively. The concentrations of 4-ene-VPA, VPA, ALT, and AST in the polytherapy group were much higher than those in the monotherapy group (All P<0.05). In the monotherapy group, the ALT and AST levels in patients younger than or equal to 2 years old were significantly higher than those over 2 years old (P<0.001). In the polytherapy group, the levels of AST, WBC, and PLT in patients younger than or equal to 2 years old were higher than those over 2 years old (P<0.05). The levels of AST did not show positive correlation with the concentrations of 4-ene-VPA and VPA (r=0.031, r=0.035, all P>0.05), and the levels of ALT also did not show positive correlation with the concentrations of 4-ene-VPA and VPA (r=-0.064, r=-0.089, all P>0.05). Conclusion: VPA may affect blood routine indexes. Age and combination therapy with the non-enzyme-induced anti-epileptic drugs are risk factors for VPA-related liver dysfunctions and renal impairment. The determination of VPA and 4-ene VPA is not a suitable tool for early warning of the VPA-induced liver dysfunction.