Welch R M, Findlay J W
Drug Metab Rev. 1981;12(2):261-77. doi: 10.3109/03602538108994032.
The present report briefly discusses some of the morphological, physiological, and compositional aspects of animal and human breast milk and how these characteristics might be important for the accumulation of drugs and foreign compounds. In addition, a study is described confirming the presence of caffeine, codeine, morphine, phenacetin, acetaminophen, and salicylic acid in the breast milk of a lactating mother following oral administration of a combination analgesic containing aspirin, phenacetin, caffeine, and codeine. Although the study is limited to one subject, it has provided critically needed data on the rates of appearance in, and elimination of these drugs from, breast milk. A similar amount of information is presented on phenacetin, also a component of the analgesic mixture, which has not been previously reported to enter human milk. The distribution of these drugs between the slightly more acidic breast milk and the relatively neutral plasma is consistent with their weakly basic, acidic, or relatively neutral properties. In general, the study shows that codeine and morphine milk concentrations are higher than, salicylic acid milk levels are much lower than, and phenacetin, caffeine, and acetaminophen milk concentrations are relatively similar to their respective plasma levels. It is projected, from estimated steady-state milk concentrations of the drugs and their metabolites studied, that very low percentages of the therapeutic dosages (less than 0.7%) would be excreted in mother's milk, too low an amount to be clinically significant to the infant.
本报告简要讨论了动物和人类母乳的一些形态、生理及成分方面的特征,以及这些特征对于药物和外来化合物蓄积的重要性。此外,还描述了一项研究,该研究证实在一位哺乳期母亲口服含阿司匹林、非那西丁、咖啡因和可待因的复合镇痛药后,其母乳中存在咖啡因、可待因、吗啡、非那西丁、对乙酰氨基酚和水杨酸。尽管该研究仅限于一名受试者,但它提供了关于这些药物在母乳中的出现率和消除率的急需数据。关于同样是该镇痛混合物成分的非那西丁,也给出了类似数量的信息,此前尚未有其进入人乳的报道。这些药物在略呈酸性的母乳和相对中性的血浆之间的分布与它们弱碱性、酸性或相对中性的性质相符。总体而言,该研究表明,可待因和吗啡在母乳中的浓度高于,水杨酸在母乳中的水平远低于,而非那西丁、咖啡因和对乙酰氨基酚在母乳中的浓度与它们各自在血浆中的水平相对相似。根据所研究药物及其代谢物的估计稳态母乳浓度推测,治疗剂量中极低的百分比(低于0.7%)会排泄到母乳中,这一量对婴儿的临床意义太小。