期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 103, 期 10, 页码 3342-3348出版社
WILEY-BLACKWELL
DOI: 10.1002/jps.24138
关键词
drug transfer into milk; lactation; organic cation transporter; solute carrier 22a; pediatric; mammary transport; secretion; disposition
资金
- Japan Research Foundation for Clinical Pharmacology
- Ministry of Education, Science and Culture of Japan [22136015]
- Grants-in-Aid for Scientific Research [22136001, 22136015] Funding Source: KAKEN
Drug transfer into milk is a general concern during lactation. So far, breast cancer resistance protein (Bcrp) is the only transporter known to be involved in this process, whereas participation of other transporters remains unclear. We investigated the importance of organic cation transporter (Oct) in drug transfer into milk in mice. The mammary glands of lactating versus nonlactating FVB strain mice revealed elevated mRNA levels of Oct1 and Bcrp, whereas Oct2 and Oct3 mRNA levels were decreased. Specific uptake of cimetidine, acyclovir, metformin, and terbutaline was observed in human embryonic kidney 293 cells transfected with murine Oct1 or Oct2. The milk-to-plasma concentration ratio (M/P) values of cimetidine and acyclovir were significantly decreased in Bcrp knockout and Oct1/2 double-knockout (DKO) mice compared with control FVB mice, whereas the M/P values of terbutaline and metformin were significantly decreased in Oct1/2 DKO mice alone. These are the first to suggest that Oct1 might be involved in secretory transfer of substrate drugs into milk. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3342-3348, 2014
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