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首页> 外文期刊>Journal of Pharmacy and Pharmaceutical Sciences >The Single Dose Poloxamer 407 Model of Hyperlipidemia; Systemic Effects on Lipids Assessed Using Pharmacokinetic Methods, and its Effects on Adipokines
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The Single Dose Poloxamer 407 Model of Hyperlipidemia; Systemic Effects on Lipids Assessed Using Pharmacokinetic Methods, and its Effects on Adipokines

机译：高脂血症的单剂量泊洛沙姆407模型;使用药代动力学方法评估对脂质的全身作用及其对脂肪因子的影响

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Purpose: The induction of hyperlipidemia using poloxamer 407 (P407) is gaining use for studying the effect of the condition on drug pharmacokinetics. Although a single intraperitoneal dose of P407 causes a rapid onset of hyperlipidemia, the initial lipid concentrations are much higher than seen in humans. The hyperlipidemia is also reversible in nature. Here, pharmacokinetic methods were used to assess the P407 dose response on serum lipids, adipokines and cytokines. Methods: Single 0.5 and 1 g/kg doses of P407 were injected into rats followed by blood collection at various times for up to 12 d. Serum was assayed for lipids, selected adipokines and cytokines. Results: As expected, large increases in lipid levels were seen by 36 h after dosing. Using area under the concentration vs. time curve as a measure of systemic lipid exposure, P407 increased serum baseline corrected serum lipids in a nearly dose proportional fashion. The maximum increase in lipids was observed at ~36 h, with most lipids remaining elevated for up to ~180 h, although for the 1 g/kg dose triglyceride concentrations had still not quite returned to baseline by 12 days postdose. In addition to changes in lipids, P407 significantly increased serum leptin and decreased the serum adiponectin concentrations but did not affect cytokine levels. Conclusion: Depending on study aims, for the use of the model it may be beneficial to perform single-dose assessments at time points later than 36 h when the lipoprotein concentrations will be more similar to those seen in patient with hyperlipidemia. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on on the issue’s contents page.
机译：目的：使用泊洛沙姆407（P407）诱导高脂血症正在用于研究该疾病对药物药代动力学的影响。尽管腹膜内单一剂量的P407会导致高脂血症的快速发作，但最初的脂质浓度比人类所见的要高得多。高脂血症本质上也是可逆的。在这里，药代动力学方法被用来评估对血清脂质，脂肪因子和细胞因子的P407剂量反应。方法：将0.5和1 g / kg剂量的P407分别注射到大鼠中，然后在不同时间采血长达12 d。测定血清中的脂质，选择的脂肪因子和细胞因子。结果：如预期的那样，给药后36 h血脂水平大幅增加。使用浓度-时间曲线下的面积作为全身脂质暴露的量度，P407以接近剂量比例的方式增加血清基线校正的血清脂质。在〜36 h时观察到最大的脂质增加，大多数脂质在〜180 h内仍保持升高，尽管对于1 g / kg剂量，甘油三酸酯浓度在给药后12天仍未完全回到基线。除脂质变化外，P407还显着增加血清瘦素并降低血清脂联素浓度，但不影响细胞因子水平。结论：根据研究目的，对于模型的使用，在脂蛋白浓度将与高脂血症患者中观察到的脂蛋白浓度更相似的36小时后的时间点进行单剂量评估可能是有益的。本文对发布后审查开放。已注册的读者（请参阅“针对读者”）可以通过单击问题的内容页面来发表评论。

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