Association of Valproic Acid and 2-propyl-4-pentenoic Acid Concentrations With Adverse Reaction in 254 Chinese Patients With Epilepsy

Hongying Ma, Wu Zhu, Can Wang, Jing Pan, Xue Yang, Jian Luo, Ping Wang

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2019 Jul 28;44(7):775-783.

PMID: 31413215

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.

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AS26413	Propyl 4-hydroxybenzoate-ring-13C6 solution			Price