Lymphatic absorption of hypolipidemic compound, 1-O-(p-(myristyloxy)-.ALPHA.-methylcinnamoyl) glycerol (LK-903).

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Abstract
The intestinal absorption process of 1-O-[p-(myristyloxy)-.alpha.-methylcinnamoyl] glycerol (LK-903), a new hypolipidemic compound, was studied in rats. When 3H-LK-903 or 3H-LKA [3H-p(myristyloxy)-.alpha.-methyl cinnamic acid], labeled at the cinnamic acid moiety, or 14C-LK-903, labeled at the glycerol moiety, were administered orally to thoracic duct-cannulated rats at a dose of 0.233 mmol/kg, 31.1, 6.7 and 18.1% of the dose, respectively, appeared in the lymph within 24 h. In this case, radioactive compunds in the lymph lipids consisted of LKA (radioactivity was not detected in the fraction of LKA with 14C-LK-903), LK-903, diglyceride analogues and triglyceride analogues. The percentages of the triglyceride analogues were the highest, followed by the diglyceride analogues. On the other hand, when doubly labeled LK-903 (3H/14C = 1, corrected ratio) was administered orally, the values of 3H/14C for the monoglyceride, diglyceride and triglyceride analogues in the lymph were 1.2-1.5, 1.7-1.9 and 1.9-2.7, respectively. The lymphatic absorption of LK-903 was stimulated by the presence of lecithin but inhibited by a high dose of triolein. The results indicated that (1) LK-903 formed micelles in the intestine, (2) a large part of LK-903 was absorbed as such, (3) a part of LK-903 was hydrolyzed in the intestinal mucosa, and (4) a part of LKA formed by hydrolysis was again utilized to synthesize the higher glycerides and absorbed via the lymphatic absorption route for lipids.