ヒグチ　ケイ   Higuchi Kei   樋口　慧    所属   東邦大学  薬学部 薬学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Evaluation of rat in vivo fetal-to-maternal transfer clearances of various xenobiotics by umbilical perfusion.
掲載誌名	正式名：Journal of pharmaceutical sciences ISSNコード：0022-3549/1520-6017
掲載区分	国外
出版社	WILEY-BLACKWELL
巻・号・頁	102(9),pp.3356-63
著者・共著者	Tomohiro Nishimura,Tatsuya Takanohashi,Masatoshi Tomi,Miho Horikoshi,Kei Higuchi,Yoshimichi Sai,Emi Nakashima
発行年月	2013/09
概要	It is important to address the tissue permeability of drugs, particularly in tissues that have a blood-tissue barrier, in terms of both lipophilicity and the contribution of transporters. Here, we employed umbilical perfusion in rats to evaluate in vivo fetal-to-maternal transfer clearances of various xenobiotics. We measured fetal-to-maternal clearance (CLfm ) of 23 compounds, which have a broad range of lipophilicity. Drugs for which CLfm was more than 300 µL/(mL min) belonged exclusively to Biopharmaceutical Drug Disposition Classification System (BDDCS) class 1 (highly permeable) and those for which CLfm was less than 50 µL/(mL min) belonged exclusively to BDDCS class 3 (poorly permeable). For most drugs, CLfm values were broadly consistent with lipophilicity. However, CLfm of digoxin was saturable and was inhibited by verapamil, suggesting that P-glycoprotein (P-gp)-mediated efflux has a substantially effect on measured clearance. CLfm of mitoxantrone continued to increase slightly at high concentrations of mitoxantrone, but placental-to-maternal clearance of mitoxantrone was saturable, implying that Bcrp1 contributes to mitoxantrone efflux across the placenta. Thus, we measured CLfm by umbilical perfusion and examined the relationship between CLfm and lipophilicity of xenobiotics. Fetal-to-maternal transport clearances measured in this study will be helpful to understand the characteristics of the blood-placental barrier.
DOI	10.1002/jps.23551
PMID	23620249