Ziv G, Sulman F G
J Dairy Sci. 1975 Nov;58(11):1637-44. doi: 10.3168/jds.S0022-0302(75)84762-X.
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.
将39种抗生素从非泌乳期奶牛乳腺的吸收情况与作为参照的[碳 - 14]尿素的吸收情况进行了比较。在乳腺内注入后的最初8至12小时内,尿素和大多数抗生素的吸收符合一级动力学。多粘菌素B、黏菌素、新霉素、螺旋霉素以及几种四环素的吸收呈双指数形式。似乎决定药物从乳腺吸收情况的物理化学性质是非离子化部分的脂溶性程度和解离常数。抗生素与蛋白质的结合也会影响吸收。对于在pH 6.8的乳汁中主要呈解离状态的药物,脂溶性是限速因素。这些化合物的吸收速率与其非离子化部分的脂溶性程度相关。对于高度脂溶性的药物,乳汁中非离子化分子的浓度是限速因素。许多结构相关抗生素以及其他结构和物理性质各异的抗生素的研究结果,使人们更加确信抗生素是通过非离子(被动)扩散从乳腺吸收的这一假设。血乳屏障对这些药物而言就如同一层惰性类脂膜。