Transport sanguin et mode d’action d’un médicament hypolipidémiant apparenté au Clofibrate: Le G P 45.699

Abstract

G P 45.699 is a chemical hypolipidemic agent related to Clofibrate. The present study, achieved in man during a clinical assay, shows that the drug, after its intestinal absorption, is carried in blood by serum albumin, and also by low density lipoproteins, chiefly density 1.006–1.063 lipoproteins. In 4 normal subjects, the drug is found to be bound to albumin for 93–98%; to low density lipoproteins for only 2–6%. But when molecular weights are considered, the mole ratio of the drug per mole of albumin is less than 1, whereas per mole of lipoprotein it reaches 13 and even 25. Similar results were obtained in 4 hyperlipidemic subjects. This ability of low density lipoproteins to transport G P 45.699 in vivo was confirmed in vitro by the ability of purified β lipoproteins to bind the drug in saline. The presence of the drug on low density lipoproteins allows a new hypothesis concerning the hypolipidemic action of G P 45.699 and of related chemical compounds, Clofibrate being the best known. According to this hypothesis, the drug when binding with peptide B (apo-β-lipoprotein) within the mucosal cell, would reduce its ability to bind and transport triglycerides and cholesterol. A direct interaction between the drug and lipoproteins would fit better with its effects on lipidemia. Its interaction with albumin being responsible for some other effects, such an interference with several antivitamine-K anticoagulants.

Effects of Antivitamin K on Hypolipemic Agents in Rat

“…This would result in an increase in the localization of thyroxine in the liver, and thus, in an increase of lipid catabolism. For Beaumont et al [1] the hypolipémie molecule should be bound to /5-lipoproteins, responsible for a shift in the lipid molecules carried out by these lipoproteins. This last hypothesis might explain the dissociation between the effects on lipemia and the anticoagulants of these hypolipémie substances.…”