Precipitation by Neomycin Compounds of Fatty Acid and Cholesterol from Mixed Micellar Solutions

Abstract The effect of the polybasic antibiotic neomycin on micellar solutions of labelled lipids and bile salts was studied both in vitro and in vivo. The addition of neomycin sulphate to simple micellar solutions of bile salts in vitro raised the pH of precipitation of the glycine conjugates and induced precipitation of the taurine conjugates of dihydroxy bile acids, but had no effect on the corresponding trihydroxy compounds. Addition of neomycin to mixed micellar solutions caused precipitation of most of the fatty acid, monglyceride and cholesterol, but a lesser proportion of bile salt. Precipitation of mixed micellar solutions by neomycin was conditional on the presence of fatty acid and progressively lessened above pH 6.5. Two basic derivatives, Compound R. I. T. 1,291 and N-methyl neomycin, also precipitated fatty acid, in contrast to the neutral compound X-acetyl neomycin. In vivo the uptake of labelled oleic acid and cholesterol from mixed micelles, one hour after intraduodenal administration to rats, was markedly decreased by the simultaneous administration of neomycin sulphate 10 to 50 mg. Similarly, in rats with cannulated intestinal lymphatics and bile ducts, the lymphatic transport of labelled fatty acid and cholesterol was also inhibited by neomycin, although this had no effect on the absorption and biliary re-excretion of labelled taurocholate and taurodeoxycholate. These results suggest that basic neomycin compounds precipitate mixed micellar solutions primarily by their ionic interaction with fatty acids, and thus can interfere with the absorption of both fat and cholesterol.