[Insecticides in metabolism. XII. Isolation and identification of metabolites of aldrin-C 14 from the urine of rabbits].
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Animals↗
Biomedical subjects
W Kochen
Publications and source records attributed to W Kochen.
[Hepatotoxicity of valproic acid treatment].
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.
Child, Preschool↗
Fatal liver failure in 16 children with valproate therapy.
The data of 16 children who died while receiving valproate (VPA) therapy in West Germany were analyzed. Five were normally developed, 5 were receiving VPA-monotherapy, and only 2 patients were aged less than 3 years. The first clinical symptoms of impending hepatotoxicity usually included nausea, vomiting, and apathy; pathologic laboratory tests reflected liver failure. Liver histology revealed microvesicular steatosis, cell necrosis, and bile duct proliferation of varying degree. An abnormal metabolite, 4-ene-VPA, was detected in all examined patients (six of six) and persisted after drug withdrawal. The pathogenesis of fatal liver failure during VPA treatment remains unknown. World-wide, approximately 100 fatalities have been reported in relation to VPA treatment. More than 90% were aged less than 20 years, 95% developed their first symptoms within the first 6 months of treatment, and 16 were treated with VPA alone. Since it is difficult precisely to define a group at risk for fatalities with VPA, careful clinical and laboratory monitoring with a special focus on vomiting and apathy, liver enzymes, and coagulation tests seem mandatory during the first 6 months after introduction of VPA. Taking into account the considerable number of fatalities during VPA treatment, the indication for its use requires careful reevaluation.
Adolescent↗