title: Hypolipidaemic activity of a novel acyclic ansamycin derivative. Synthesis and pharmacokinetic and pharmacodynamic studies in rodents.
abstract: Certain classes of the antibacterial agent rifamycin SV have recently been shown to possess marked hypolipidaemic activity. An acyclic oxazolylrifamycin has been prepared and its hypolipidaemic properties evaluated; it was found to be significantly more potent when administered orally to Wistar and Sprague-Dawley rats than other previously described rifamycin hypolipidaemics. The plasma decay rate of a bolus of intravenously administered 125I-LDL (low density lipoprotein) was significantly greater in treated rats than in rats receiving vehicle alone, compatible with a drug-induced increase in LDL catabolism. A bolus of radiolabelled drug was rapidly removed from the circulation by the liver, the presumed target organ. Compound 3 constitutes the first example of a new class of acyclic hypolipidaemic ansamycins.
authors.affiliation: Ciba-Geigy Pharmaceuticals, Horsham, West Sussex, UK.
authors.forename: K A
authors.initials: KA
authors.lastname: Menear
authors.forename: K E
authors.initials: KE
authors.lastname: Dunnet
authors.forename: J G
authors.initials: JG
authors.lastname: Hastewell
authors.forename: H G
authors.initials: HG
authors.lastname: Eichler
authors.forename: J C
authors.initials: JC
authors.lastname: Gibson
authors.forename: E F
authors.initials: EF
authors.lastname: Kimble
authors.forename: W
authors.initials: W
authors.lastname: Kump
authors.forename: P W
authors.initials: PW
authors.lastname: Taylor
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D006949:Hyperlipidemias / Q000097:blood; D000960:Hypolipidemic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008826:Microbial Sensitivity Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012294:Rifamycins / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000960:Hypolipidemic Agents; D047029:Lactams, Macrocyclic; D008075:Lipoproteins, HDL; D012294:Rifamycins; D002784:Cholesterol