Association of valproic acid and 2-propyl-4-pentenoic acid concentrations with adverse reaction in 254 Chinese patients with epilepsy / 中南大学学报(医学版)

ABSTRACT

Objective: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 ofVPA (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.