Neuvonen P J
Drugs. 1976;11(1):45-54. doi: 10.2165/00003495-197611010-00004.
All tetracycline derivatives are bacteriostatics and their concentration in serum should not fall during the therapy below the generally accepted minimum therapeutic concentration of 0.5 to 1.5 mug/ml. Tetracyclines have a high affinity to form chelates with polyvalent metallic cations such as Fe+++, Fe++, Al+++, Mg++ and Ca++. Many of these tetracycline-metal complexes are either insoluble or otherwise poorly absorbable from the gastro-intestinal tract. Milk and other dairy products, antacids containing polyvalent cations, as well as various iron salts ingested simultaneously with tetracycline derivatives, might interfere with their absorption by 50 to 90% or even more. The severity of interaction depends both on the nature of the tetracycline derivative and of the cation, on the doses used, on pharmaceutical factors, and on time schedules in dosing. An interval of 3 hours between the ingestion of tetracyclines and cations prevents the interaction. The pharmacokinetic interactions in absorption of tetracyclines likely to be clinically significant in cases where the infecting pathogens are moderately resistant to tetracyclines and relatively high serum concentrations are needed for proper bacteriostasis.
所有四环素衍生物均为抑菌剂，治疗期间其血清浓度不应降至公认的最低治疗浓度0.5至1.5微克/毫升以下。四环素与多价金属阳离子（如Fe+++、Fe++、Al+++、Mg++和Ca++）形成螯合物的亲和力很高。许多这些四环素-金属络合物要么不溶，要么从胃肠道的吸收性很差。牛奶和其他乳制品、含有多价阳离子的抗酸剂以及与四环素衍生物同时摄入的各种铁盐，可能会使其吸收减少50%至90%甚至更多。相互作用的严重程度取决于四环素衍生物和阳离子的性质、所用剂量、药物因素以及给药时间表。四环素和阳离子摄入之间间隔3小时可防止相互作用。在感染病原体对四环素中度耐药且需要相对较高血清浓度以实现适当抑菌的情况下，四环素吸收中的药代动力学相互作用可能具有临床意义。
