Hypolipidaemic activity of a novel acyclic ansamycin derivative. Synthesis and pharmacokinetic and pharmacodynamic studies in rodents.
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.
Menear
K A
KA
Ciba-Geigy Pharmaceuticals, Horsham, West Sussex, UK.
Dunnet
K E
KE
Hastewell
J G
JG
Eichler
H G
HG
Gibson
J C
JC
Kimble
E F
EF
Kump
W
W
Taylor
P W
PW
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
D000900:Anti-Bacterial Agents; D000960:Hypolipidemic Agents; D047029:Lactams, Macrocyclic; D008075:Lipoproteins, HDL; D012294:Rifamycins; D002784:Cholesterol