Children's toxicology from bench to bed - Liver Injury (1): Drug-induced metabolic disturbance - Toxicity of 5-FU for pyrimidine metabolic disorders and pivalic acid for carnitine metabolism

研究成果: Article査読

7 被引用数 (Scopus)

抄録

Congenital disorders of metabolism show a wide spectrum of symptoms as a consequence of impairment of a certain metabolic pathway by mutated enzymes resulting in abnormal accumulation of enzyme substrates, deficiency of expected products, and abnormal burden to collateral metabolic pathways, etc. However, in some occasions, depending on which pathway up to what degree of disturbance, it can be asymptomatic until a certain kind of burden is placed on to the patient. Enzyme deficiency involved in pyrimidine degradation, such as Dihydropyrimidine dehydrogenase (DPD) and Dihydropyrimidinase (DHP), has been reported with convulsion or autism as symptoms, but many asymptomatic cases are also reported. However, when the patients are treated with 5-fluorouracil, a pyrimidine analogue anticancer drug, lethal side-effects can be seen even in asymptomatic patients. Some oral cephem antibiotics have pivalic acid side chain to increase absorption rate at intestine. These antibiotics degrade into active antibiotics and pivalic acid at the intestinal wall. This pivalic acid is carnitine-conjugated and excreted into urine. Carnitine acts as a carrier of long chain fatty acid to mitochondria and to beta-oxidation, thus an important molecule for energy production by beta-oxidation and maintenance of mitochondrial function. Because of this, long term administration of such antibiotics could induce depletion of carnitine from the body and lead to low ketotic hypoglycemia, convulsion and consciousness disturbance. This paper reports some possible serious side effects closely linked to drug metabolism.

本文言語English
ページ(範囲)SP217-SP222
ジャーナルJournal of Toxicological Sciences
34
2 SPEC. ISS.
DOI
出版ステータスPublished - 2009
外部発表はい

All Science Journal Classification (ASJC) codes

  • Toxicology

フィンガープリント 「Children's toxicology from bench to bed - Liver Injury (1): Drug-induced metabolic disturbance - Toxicity of 5-FU for pyrimidine metabolic disorders and pivalic acid for carnitine metabolism」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル