Keulen F P, Kochen W
Klin Padiatr. 1985 Sep-Oct;197(5):431-6. doi: 10.1055/s-2008-1034017.
Hepatotoxicity of valproic acid (VPA) is reported in a psychomotor retarded boy. A four-month antiepileptic therapy was followed by a combined VPA/phenytoin treatment where-upon, two months later, the patient died in a hepatic coma. In the final state the metabolic pattern of VPA was still found within the normal range with the exception of the two abnormal metabolites 4-en-VPA) (2-propyl-4-pentenoic acid) and 4.4'-dien-VPA (2-(2-propenyl-4-pentenoic acid) detected only in low concentration. The amino acid pattern in plasma was characterized by a decrease or branched chain amino acids by 50% in contrast to the increase of the aromatic amino acids. Methionine, however, was in the normal range. Due to lack of a biochemical parameter indicating a possibly irreversible development of VPA induced hepatotoxicity stopping of VPA therapy should be obligatory if abnormal unsaturated VPA metabolites are detected or if dien-VPA/3, a normal metabolic compound, is increased above the normal range. L-carnitine treatment is recommended as a prophylactic therapy.
据报道，一名精神运动发育迟缓的男孩出现了丙戊酸（VPA）肝毒性。在进行了四个月的抗癫痫治疗后，该患者接受了VPA/苯妥英联合治疗，两个月后，患者死于肝昏迷。在终末期，除了仅以低浓度检测到的两种异常代谢物4-烯-VPA（2-丙基-4-戊烯酸）和4,4'-二烯-VPA（2-(2-丙烯基)-4-戊烯酸）外，VPA的代谢模式仍在正常范围内。血浆中的氨基酸模式表现为支链氨基酸减少50%，而芳香族氨基酸增加。然而，蛋氨酸处于正常范围。由于缺乏表明VPA诱导的肝毒性可能不可逆转发展的生化参数，如果检测到异常的不饱和VPA代谢物，或者正常代谢化合物二烯-VPA/3增加超过正常范围，则必须停止VPA治疗。建议使用L-肉碱治疗作为预防性治疗。
