title: Synthesis of highly water-soluble fibrate derivatives via BGLation.
abstract: Three water-soluble fibrates (fenofibrate, bezafibrate and chlofibrate) conjugated with a symmetrically branched glyceryl trimer (BGL003) were synthesized, and an evaluation of the fenofibrate-BGL003 conjugate as a candidate for anti-hyperlipemia drug was carried out using rats. The water-solubility of the fenofibrate-BGL003 conjugate was several thousand times greater than that of the original fenofibrate. The lipid-lowering effects of the fenofibrate-BGL003 conjugate were as strong as those of the same grams of fenofibrate. The actual active species of fenofibrate, fenofibric acid, was detected in rats' blood, but neither the fenofibrate-BGL003 conjugate nor fenofibrate was detected, probably due to enzymatic hydrolysis of the ester bond. The plasma concentration of fenofibric acid derived from the fenofibrate-BGL003 conjugate was five times higher than that derived from fenofibrate 4h after administration.
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Health Biosciences, Graduate School of The University of Tokushima, Tokushima, Japan. nem@ph.tokushima-u.ac.jp
authors.forename: Hisao
authors.initials: H
authors.lastname: Nemoto
authors.forename: Masaki
authors.initials: M
authors.lastname: Kamiya
authors.forename: Aki
authors.initials: A
authors.lastname: Nakamoto
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Kosuke
authors.initials: K
authors.lastname: Matsumura
authors.forename: Hatsuhiko
authors.initials: H
authors.lastname: Hattori
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kawamura
authors.forename: Chiaki
authors.initials: C
authors.lastname: Taoka
authors.forename: Shinji
authors.initials: S
authors.lastname: Abe
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ishizawa
authors.forename: Licht
authors.initials: L
authors.lastname: Miyamoto
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuchiya
mesh_terms: D000818:Animals; D001629:Bezafibrate / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002994:Clofibrate / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011345:Fenofibrate / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014280:Triglycerides / Q000097:blood; D014867:Water / Q000737:chemistry
chemical_list: D000960:Hypolipidemic Agents; D014280:Triglycerides; D014867:Water; D002994:Clofibrate; D011345:Fenofibrate; D001629:Bezafibrate