Studies on Drug-induced Lipidosis:VI. Identification and Determination of the Drug and Its Metabolite in Lipidosis Induced by 4, 4'-Diethylaminoethoxyhexestrol

  • MATSUZAWA Yuji
    The Second Department of Internal Medicine, Osaka University Medical School
  • YOKOMURA Tohru
    The Second Department of Internal Medicine, Osaka University Medical School
  • ISHIKAWA Katsunori
    The Second Department of Internal Medicine, Osaka University Medical School
  • ADACHI Susumu
    The Second Department of Internal Medicine, Osaka University Medical School
  • YAMAMOTO Akira
    The Second Department of Internal Medicine, Osaka University Medical School

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説明

In clinical cases of lipidosis or foam cell syndrome caused by an administration of 4, 4'-diethylaminoethoxyhexestrol, the drug was found to accumulate in liver and some other tissues. In liver specimens obtained from patients who had been administered this drug at a level of 75-150 mg per day for more than 6 months, the concentration of the drug remaining in the liver was 0.21-0.74 percent of the wet weight of the tissue. Molar ratio of the sum of the drug and free cholesterol to the sum of the acidic phospholipids was 2.11±0.83. The results suggested that the drug was participating in the formation of myeline-like structure together with acidic phospholipids and free cholesterol.<br> The drug metabolite in rat liver was extracted and purified by phase partitioning and preparative TLC. Instrumental analysis by infra-red spectroscopy, nuclear magnetic resonance and mass spectroscopy showed that the major metabolite in rat liver was a derivative of 4, 4'-diethylaminoethoxyhexestrol which had one hydroxyl group in the benzene ring. It was concluded that rat liver has an ability to oxidize the drug, while human livers lack in this ability.

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