Absorption of antibiotics by the bovine udder

Absorption of 39 antibiotics from the nonlactating bovine udder was compared with absorption of [carbon-14] urea as reference. First order kinetics characterized the absorption of urea and most of the antibiotics during the first 8 to 12 h after intramammary infusion. The absorption of polymyxin B, colistin, neomycin, spiramycin, and several tetracyclines was biexponential. The physicochemical properties of drugs which appeared to govern their absorption from the udder were the degree of lipid-solubility of the nonionized fraction and the dissociation constant. Antibiotic protein binding also influenced absorption. Lipid-solubility was the rate-limiting factor with drugs that are mainly dissociated in milk at pH 6.8. These compounds were absorbed at rates related to their degree of lipid-solubility of nonionized fraction. The concentration of the nonionized molecule in milk was the rate-limiting factor with drugs that were highly lipid-soluble. Results with a number of structurally-related antiobiotics, and with others of diverse structures and physical properties, added considerable confidence to the assumption that antibiotics are absorbed from the udder by nonionic (passive) diffusion. The blood-milk barrier behaves as an inert lipoid membrane to these drugs.