title: Organic cation transporter/solute carrier family 22a is involved in drug transfer into milk in mice.
abstract: 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.
authors.affiliation: Department of Pediatrics, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ito
authors.forename: Kousei
authors.initials: K
authors.lastname: Ito
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ikebuchi
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyata
authors.forename: Yu
authors.initials: Y
authors.lastname: Toyoda
authors.forename: Tappei
authors.initials: T
authors.lastname: Takada
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hisaka
authors.forename: Masashi
authors.initials: M
authors.lastname: Honma
authors.forename: Akira
authors.initials: A
authors.lastname: Oka
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kusuhara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008892:Milk / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000097:blood / Q000378:metabolism*; D010599:Pharmacokinetics
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D017931:DNA Primers; D027701:Organic Cation Transport Proteins; D004364:Pharmaceutical Preparations
keywords: disposition; drug transfer into milk; lactation; mammary transport/secretion; organic cation transporter/solute carrier 22a; pediatric