Studies on Drug-induced Lipidosis

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. 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.