Disposition of etofibrate, clofibric and nicotinic acid esters, and their products in dogs.
Etofibrate, the ethylene glycol diester of clofibric and nicotinic acids, on intravenous infusion into dogs, has a terminal half-life of 2 min. The intermediate half-esters, the nicotinate and the clofibrate, have respective terminal half-lives of 4.6 and 1.7 min and appear fleetingly when etofibrate is administered. In contrast to the 42-h terminal half-life of clofibric acid, the other final transformation product, nicotinic acid, shows saturable or dose-dependent pharmacokinetics in dogs that conform to the Michaelis-Menten equation with a terminal half-life of 4.4 min at low concentrations (less than 6.9 microM/kg). Three distinct metabolites of nicotinic acid can be identified and assayed chromatographically in the urine. The partition properties were similar to nicotinic acid. Nicotinic acid is excreted 30% unchanged into urine with a renal clearance of 70 mL/min in 27-kg dogs.
D000818:Animals; D002994:Clofibrate / Q000031:analogs & derivatives*; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004285:Dogs; D004952:Esters / Q000378:metabolism; D006207:Half-Life; D000960:Hypolipidemic Agents / Q000378:metabolism*; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D009525:Niacin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D012995:Solubility; D012997:Solvents; D013997:Time Factors
D004952:Esters; D000960:Hypolipidemic Agents; D012997:Solvents; C009746:etofibrate; D009525:Niacin; D002995:Clofibric Acid; D002994:Clofibrate