Sugimoto T, Muro H, Woo M, Nishida N, Murakami K
Department of Pediatrics, Kansai Medical University Otokoyama Hospital, Kyoto, Japan.
Epilepsia. 1996 Dec;37(12):1200-3. doi: 10.1111/j.1528-1157.1996.tb00553.x.
We wished to determine the relation between liver function, beta-, and omega-, and omega-1-oxidation metabolites and 4-en-valproate (VPA).
We measured the serum levels of VPA and its metabolites in children and adolescent receiving high-dose VPA plus phenytoin (PHT) therapy using gas chromatography-mass spectrometry with selected ion monitoring (GC/MS/ SIM).
In high-dose VPA plus PHT polytherapy, the total VPA serum concentration was distinctly low, the concentrations of total beta-oxidation metabolites were decreased, the percentage values of VPA (percent of VPA) of total beta-oxidation metabolites were increased, and the E-2-en-VPA/3-keto-VPA ratios were decreased, as compared with those in high-dose VPA monotherapy. In high-dose VPA plus PHT polytherapy, 4-en-VPA (microM) was decreased and the concentrations of [omega + (omega-1)]-oxidation metabolites (microM) were decreased as compared with those in high-dose VPA monotherapy. In high-dose VPA plus PHT, serum glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and lactic dehydrogenase (LDH) did not correlate significantly with the ¿beta/omega + (omega-1)¿ metabolites ratio and 4-en-VPA levels, but serum GOT, GPT, and LDH were increased as compared with those in high-dose VPA therapy. We were not able to establish a significant relation between the formation of metabolites of VPA metabolites and liver dysfunction in patients receiving high-dose VPA and PHT concurrently.
Metabolic levels do not appear to be a reliable predictor of hepatotoxicity in children receiving pharmacological antiepileptic drug (AED) therapy.
我们希望确定肝功能、β-、ω-和ω-1-氧化代谢物与4-烯丙戊酸（VPA）之间的关系。
我们使用气相色谱-质谱联用选择离子监测法（GC/MS/SIM）测量了接受高剂量VPA加苯妥英（PHT）治疗的儿童和青少年血清中VPA及其代谢物的水平。
与高剂量VPA单药治疗相比，在高剂量VPA加PHT联合治疗中，VPA血清总浓度明显较低，总β-氧化代谢物浓度降低，总β-氧化代谢物中VPA的百分比值（VPA百分比）增加，E-2-烯丙戊酸/3-酮戊酸比率降低。与高剂量VPA单药治疗相比，在高剂量VPA加PHT联合治疗中，4-烯丙戊酸（微摩尔）降低，[ω+（ω-1）]-氧化代谢物（微摩尔）浓度降低。在高剂量VPA加PHT治疗中，血清谷草转氨酶（GOT）、谷丙转氨酶（GPT）和乳酸脱氢酶（LDH）与“β/ω+（ω-1）”代谢物比率和4-烯丙戊酸水平无显著相关性，但与高剂量VPA治疗相比，血清GOT、GPT和LDH升高。我们无法在同时接受高剂量VPA和PHT治疗的患者中建立VPA代谢物形成与肝功能障碍之间的显著关系。
代谢水平似乎不是接受抗癫痫药物（AED）治疗的儿童肝毒性的可靠预测指标。
