Wout Z G, Pec E A, Maggiore J A, Williams R H, Palicharla P, Johnston T P
Department of Pharmaceutics, College of Pharmacy, University of Illinois, Chicago.
J Parenter Sci Technol. 1992 Nov-Dec;46(6):192-200.
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 animals 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.(ABSTRACT TRUNCATED AT 250 WORDS)
泊洛沙姆（普朗尼克）非离子表面活性剂载体是一系列化学相关的嵌段共聚物，在肠胃外制剂中广泛用作传统低分子量有机药物分子的增溶剂和湿润剂，以及蛋白质和多肽药物的稳定剂。我们报告了泊洛沙姆407（普朗尼克F - 127）对大鼠血浆胆固醇和甘油三酯浓度的影响。通过腹腔注射（剂量 = 1.5克/千克）将泊洛沙姆407注入大鼠体内，导致持续（超过96小时）的高胆固醇血症和高甘油三酯血症。相对于总胆固醇，需要更大剂量的泊洛沙姆407才能提高血浆甘油三酯水平。食用商业大鼠饲料对对照（未注射泊洛沙姆）动物的血浆胆固醇和甘油三酯水平影响可忽略不计，但接受腹腔注射泊洛沙姆407（30% w/w）的动物进食后，其血浆胆固醇和甘油三酯的升高幅度明显（p <.05）大于禁食状态下注射泊洛沙姆407的动物。观察到泊洛沙姆407的给药途径（即肌肉注射与腹腔注射）对于泊洛沙姆诱导的血浆胆固醇升高而言，比泊洛沙姆介导的血浆甘油三酯升高是更重要的因素。我们的结果还提供了提示性证据，表明向大鼠腹腔注射泊洛沙姆407溶液（30% w/w）后导致血浆胆固醇升高的机制可能是由于泊洛沙姆载体刺激了肝脏中的3 - 羟基 - 3 - 甲基戊二酰辅酶A（HMG - CoA）还原酶活性。（摘要截短为250字）
