■静脉内脂肪乳剂被认为是局部麻醉毒性病例的抢救疗法,但其在逆转过量或与其他药物相关的毒性方面的应用仍是争论的主题。这项体外研究旨在扩大我们对分配在确定静脉脂质乳剂对水性游离药物浓度的影响中的重要性的理解。
■筛选了二十七种药物和相关代谢产物,用于静脉内脂肪乳剂减少水相中游离药物量的能力,使用专门为此目的设计的盒式磁带。测量了从血浆到磷酸盐缓冲盐水的跨膜平衡的药物的相对量,使用液相色谱-质谱,在6小时的时间点,血浆样品用静脉内脂肪乳剂和配对,未经处理的对照。
■将获得的数据相对于划分的测量值(LogP和cLogD7.4)和对数转化的非蛋白质结合的药物作图。静脉内脂肪乳剂减少磷酸盐缓冲盐水隔室中检测到的药物的能力与LogP和cLogD7.4之间存在显着负相关,并且与log[非蛋白质结合药物]直接相关。然而,许多药物在不同血浆样本之间显示出显著差异.
■水性隔室中游离药物的调节可以通过分配系数广泛预测,尽管雷米普利在这方面被认为是一个异常值。需要进一步的机理和临床探索,以建立脂质乳剂治疗的标准化方案。
UNASSIGNED: Intravenous lipid emulsion is recognised as a therapy for rescue in cases of local anaesthetic toxicity, but its use in reversing overdose or toxicity related to other drugs remains the subject of debate. This in vitro study sought to expand our understanding of the importance of partitioning in determining the impact of intravenous lipid emulsion on aqueous free drug concentrations.
UNASSIGNED: Twenty-seven drugs and associated metabolites were screened for the ability of intravenous lipid emulsion to reduce the amount of free drug in the aqueous phase, using specialised cassettes designed for this purpose. The relative amount of drug equilibrating across the membrane from plasma to phosphate-buffered saline was measured, using liquid chromatography-mass spectrometry, at a 6 h timepoint in plasma samples treated with intravenous lipid emulsion and paired, untreated controls.
UNASSIGNED: The data obtained were plotted against measures of partition (LogP and cLogD7.4) and with log-transformed non-protein bound drug. There were significant inverse correlations between the capacity for intravenous lipid emulsion to reduce drug detected in the phosphate-buffered saline compartment and LogP and cLogD7.4, and a direct association with log [non-protein-bound drug]. However, a number of drugs showed substantial variance between different plasma samples.
UNASSIGNED: Modulation of free drug in the aqueous compartment is broadly predictable by the partition coefficient, although ramipril was identified to be an outlier in this regard. Further mechanistic and clinical exploration is merited to establish a standardised protocol for lipid emulsion therapy.