Enprostil Impairs Cholesterol and Fat Absorption

BACKGROUND: Enprostil, a synthetic dehydroprostaglandin E2 structural analogue primarily developed for treatment of gastritis, has been shown also to lower serum cholesterol. METHODS: We studied cholesterol metabolism in seven hypercholesterolemic subjects before, during, and after a low-dose enprostil (18 micrograms/day) treatment, measuring serum lipids, cholesterol absorption by an oral double-isotope method, fecal cholesterol elimination by the balance technique, and fecal fat. In addition, an oral fat load test with vitamin A was performed. RESULTS: The drug treatment reduced serum concentrations of total and low-density lipoprotein (LDL) cholesterol by 8.2% and 7.9% (p < 0.05), respectively, and cholesterol absorption efficiency by 18% (p < 0.05), and increased fecal output of neutral sterols by 20% (p < 0.05), bile acids by 24% (NS), and cholesterol synthesis by 30% (p < 0.05). Postabsorptive concentrations of triglycerides and vitamin A in chylomicrons were reduced 3-4 h after the intake of the test meal. Fecal fat excretion was doubled during the enprostil treatment. CONCLUSIONS: Enprostil reduces serum cholesterol concentrations, apparently by inhibiting cholesterol absorption so that fecal cholesterol elimination is increased in association with a mild fat malabsorption. Enhanced intestinal motility may contribute to these changes, frequently causing abdominal fullness or mild pain without diarrhea.