Effects of dietary fat levels on the absorption and tissue accumulation of probucol in the rat.

The effects of dietary fat level on the absorption and tissue accumulation of probucol (PB, CAS 23288-49-5) were studied in male Wistar rats. Addition of 1% PB (w/w) to the diets as compared to the diets without an addition (P) resulted in a decrease in the concentration of both serum and high-density lipoprotein (HDL) cholesterol as well as TBA-reactive substances (TBARS), without influencing food intake or growth. When rats were fed with the PB diet, the apparent intestinal absorption of PB was 7.9%, while the serum PB level was 5 micrograms/ml. The tissue distribution of PB, when expressed per g of tissue, was highest in the adrenal glands, followed by the liver, heart, epididymal adipose tissues, kidneys, lung, spleen, and testes. The addition of 10% olive oil (PBO) to the PB diet (w/w) appeared to double the PB diet-induced increase in apparent intestinal absorption and the serum concentration of PB. Furthermore, compared with the PB diet, the PBO diet caused 3- to 4-fold higher accumulation of PB in the liver and its subcellular fractions and 2-fold higher accumulation in the spleen. However, there was no further accumulation of the drug in the heart, kidneys, lungs, and testes. Incorporation of the drugs into adipose tissues was significantly lower with the PBO diet than with the PB diet. These results suggest that dietary manipulation leads to changes in the intestinal absorption and serum level of PB.