The antihypercholesterolemic activity of candicdin as a function of dietary cholesterol in cockerels

In the first of two experiments using White Leghorn cockerels, a multifactorial analysis of variance was employed to characterize the antihypercholesterolemic responses (AHC) to candicidin (a heptaene macrolide antifungal antibiotic)-containing diets and the manner in which hypercholesterolemic challenges of different magnitudes modify these responses. In hypercholesterolemic diets, oral candicidin reduced plasma cholesterol concentration in a dose-dependent manner. The relative AHC effects of the diet were dependent on and varied directly with the presence and magnitude of the hypercholesterolemic challenge. The AHC effects of oral candicidin appeared to be additive to the homeostatic mechanisms limiting the rise in plasma cholesterol concentration induced by hypercholesterolemic diets. In the second experiment the absorption of oral 14C-candicidin was studied. Radioactivity above background levels was not found in any of the sampled tissues 4 days after administration of the 14C-candicidin pulse. The total cumulative recovery of radioactivity in the excreta was approximately 95% of the administered dose after 4 days. Within the limits of detection, oral candicidin did not appear to be absorbed from the intestine and appeared to be rapidly and quantitatively eliminated from the body in the feces. Chronic provision of candicidin appeared to increase transit time through the gastrointestinal tract.