title: VLDL/LDL acts as a drug carrier and regulates the transport and metabolism of drugs in the body.
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.
authors.affiliation: Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan. tappei-tky@umin.ac.jp.
authors.forename: Tappei
authors.initials: T
authors.lastname: Takada
authors.affiliation: Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Yamanashi
authors.affiliation: Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Osaka, 565-8565, Japan.
authors.forename: Masatsune
authors.initials: M
authors.lastname: Ogura
authors.affiliation: Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Masuo
authors.affiliation: Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Osaka, 565-8565, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Harada-Shiba
authors.affiliation: Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan. suzukihi-tky@umin.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D017311:Amlodipine / Q000493:pharmacokinetics; D000818:Animals; D001692:Biological Transport; D002784:Cholesterol / Q000097:blood; D004337:Drug Carriers; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D051379:Mice; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D013988:Ticlopidine / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D004364:Pharmaceutical Preparations; D011973:Receptors, LDL; D017311:Amlodipine; D002784:Cholesterol; D013988:Ticlopidine