RRC ID 47961
著者 Yamamoto H, Takada T, Yamanashi Y, Ogura M, Masuo Y, Harada-Shiba M, Suzuki H.
タイトル VLDL/LDL acts as a drug carrier and regulates the transport and metabolism of drugs in the body.
ジャーナル Sci Rep
Abstract Only free drugs have been believed to be carried into tissues through active or passive transport. However, considering that lipoproteins function as carriers of serum lipids such as cholesterol and triglycerides, we hypothesized that lipoproteins can associate with certain drugs and mediate their transport into tissues in lipid-associated form. Here, in vitro and in vivo studies with low density lipoprotein receptor (LDLR)-overexpressing or -knockdown cells and wild-type or LDLR-mutant mice were used to show the association of various drugs with lipoproteins and the uptake of lipoprotein-associated drugs through a lipoprotein receptor-mediated process. In clinical studies, investigation of the effect of lipoprotein apheresis on serum drug concentrations in patients with familial hypercholesterolemia demonstrated that lipoprotein-mediated drug transport occurs in humans as well as in mice. These findings represent a new concept regarding the transport and metabolism of drugs in the body and suggest that the role of lipoprotein-mediated drug transport should be considered when developing effective and safe pharmacotherapies.
巻・号 7(1)
ページ 633
公開日 2017-4-4
DOI 10.1038/s41598-017-00685-9
PII 10.1038/s41598-017-00685-9
PMID 28377633
PMC PMC5428859
MeSH Amlodipine / pharmacokinetics Animals Biological Transport Cholesterol / blood Drug Carriers* Hyperlipoproteinemia Type II / blood Hyperlipoproteinemia Type II / drug therapy Hyperlipoproteinemia Type II / metabolism Lipoproteins, LDL / metabolism* Lipoproteins, VLDL / metabolism* Male Mice Pharmaceutical Preparations / metabolism* Protein Binding Receptors, LDL / genetics Receptors, LDL / metabolism Ticlopidine / pharmacokinetics
IF 3.998
引用数 19
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
実験動物マウス GSC0247