Peroral administration of beauverolides allows their transport into the peripheral blood and urine

Beauverolides are hydrophobic cyclodepsipeptides that inhibit sterolO-acyltransferases and calmodulin, thereby reducing senile plaques in Alzheimer's disease and preventing foam cell formation in atherosclerosis. Other sterolO-acyltransferase inhibitors suffer from low bioavailability, and evidence of the distribution of beauverolides in bodily fluids is lacking. We aimed to determine the optimal formulation of beauverolides for administration to experimental animals and to determine if the orally administered beauverolides could cross the gastrointestinal barrier and be secreted in urine. We found that beauverolides formed gels in aqueous solutions and we developed a formula for their peroral administration. Administration of the beauverolide gel pellets to experimental mice revealed that beauverolides cross the gastrointestinal barrier, circulate untouched in the blood, and are excreted in the urine. Using liquid chromatography-mass spectrometry analyses, we show that the administered beauverolides circulate in mouse blood and are excreted from the body 24 h after their administration.