%0 Journal Article %A Zjumira G. M. Wout %A Edward A. Pec %A Jack A. Maggiore %A Robert H. Williams %A Prema Palicharla %A Thomas P. Johnston %T Poloxamer 407—Mediated Changes in Plasma Cholesterol and Triglycerides Following Intraperitoneal Injection to Rats %D 1992 %J PDA Journal of Pharmaceutical Science and Technology %P 192-200 %V 46 %N 6 %X Poloxamer (Pluronic®) nonionic surfactant vehicles are a series of chemically-related block copolymers finding widespread use in parenteral formulations as solubilizing and wetting agents for traditional, low-molecular weight organic drug molecules, as well as stabilizing agents for proteins and polypeptide drugs. We report the effects of poloxamer 407 (Pluronic® F-127) on plasma cholesterol and triglyceride concentrations in rats. Poloxamer 407 injected into rats by intraperitoneal injection (dose = 1.5 gm/kg) resulted in sustained (greater than 96 hour) hypercholesterolemia and hypertriglyceridemia. A larger dose of poloxamer 407 was required to elevate plasma triglyceride relative to total cholesterol. Ingestion of commercial rat chow had a negligible effect on plasma cholesterol and triglycerides levels in control (no poloxamer injection) animals, but consumption of food by animals that received an intraperitoneal injection of poloxamer 407 (30% w/w) resulted in significantly (p <.05) greater elevations in plasma cholesterol and triglycerides than in fasted animak administered poloxamer 407. The route of poloxamer 407 administration, namely intramuscular vs. intraperitoneal injection, was observed to be a more important factor for poloxamer-induced elevations in plasma cholesterol than poloxamer-mediated elevations in plasma triglycerides. Our results also provide suggestive evidence that the mechanism responsible for the elevation of plasma cholesterol following intraperitoneal injection of a poloxamer 407 solution (30% w/w) to rats may be due to stimulation of 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase activity in the liver by the poloxamer vehicle. Oral administration of lovastatin (dose = 75mg/kg/day × 3 day) to rats prior to intraperitoneal injection of a solution of poloxamer 407 (30% w/w) completely inhibited elevations in plasma cholesterol and triglycerides. Thus, this preliminary investigation has identified a vehicle which, when injected intraperitoneally to rats, produces sustained hypercholesterolemia and hypertriglyceridemia. Elevated levels of plasma cholesterol and triglycerides resulting from the chronic administration of poloxamer-containing (? 1-2% w/w) drug formulations to patients may potentially hinder therapeutic outcome. The animal model presented here for the chemical induction of hypercholesterolemia and hypertriglyceridemia in rats may represent an inexpensive, reliable, and rapid means with which to screen new chemical entities designed to inhibit HMG-CoA reductase activity and lower both total plasma cholesterol and triglycerides. %U https://journal.pda.org/content/pdajpst/46/6/192.full.pdf