Kuhara T, Inoue Y, Matsumoto M, Shinka T, Matsumoto I, Kawahara N, Sakura N
Division of Human Genetics, Kanazawa Medical University, Ishikawa, Japan.
Epilepsia. 1990 Mar-Apr;31(2):214-7. doi: 10.1111/j.1528-1167.1990.tb06309.x.
Using gas chromatography-mass spectrometry, we showed that the urinary metabolite profile of valproate (VPA) in a subject receiving VPA and phenobarbital (PB) who died of fulminant hepatic failure was quite different from those of reported patients with Reye's syndrome or fatal hepatic failure. Only 2-n-propylglutarate, the end product of omega-oxidation of VPA, was excreted in markedly increased amounts, while other VPA metabolites were undetectable. Although the primary cause of fulminant hepatitis and the mechanism of enhanced VPA metabolism by the hepatic P-450 system in this patient are not clear, our findings suggest that P-450-mediated reactions become the predominant metabolic pathway of VPA in a stage of fulminant hepatic failure.
通过气相色谱 - 质谱联用技术，我们发现，一名接受丙戊酸（VPA）和苯巴比妥（PB）治疗且死于暴发性肝衰竭的患者，其尿液中丙戊酸的代谢物谱与报道的瑞氏综合征或致命性肝衰竭患者的代谢物谱有很大不同。仅VPA ω-氧化的终产物2-正丙基戊二酸的排泄量显著增加，而其他VPA代谢物则无法检测到。虽然暴发性肝炎的主要病因以及该患者肝脏P-450系统增强VPA代谢的机制尚不清楚，但我们的研究结果表明，在暴发性肝衰竭阶段，P-450介导的反应成为VPA的主要代谢途径。
