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首页> 美国卫生研究院文献>Antimicrobial Agents and Chemotherapy >Species Differences in the Proportion of Plasma Lipoprotein Lipid Carried by High-Density Lipoproteins Influence the Distribution of Free and Liposomal Nystatin in Human Dog and Rat Plasma
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Species Differences in the Proportion of Plasma Lipoprotein Lipid Carried by High-Density Lipoproteins Influence the Distribution of Free and Liposomal Nystatin in Human Dog and Rat Plasma

机译：高密度脂蛋白携带的血浆脂蛋白脂质比例的物种差异影响人狗和大鼠血浆中游离和脂质体制霉菌素的分布

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The objective of this study was an interspecies comparison of free nystatin (NYS) and liposomal NYS (Nyotran) distribution in plasma. NYS and liposomal NYS at concentrations of 5, 10, and 20 μg of NYS/ml were incubated in human, dog, and rat plasma for 5, 60, and 180 min at 37°C. Following these incubations, plasma samples were separated into their high-density lipoprotein (HDL), triglyceride-rich lipoprotein, low-density lipoprotein, and lipoprotein-deficient plasma (LPDP) fractions by density-gradient ultracentrifugation, and each fraction was assayed for NYS by high-pressure liquid chromatography. Total plasma and lipoprotein cholesterol, triglyceride, and protein concentrations in each human, dog, or rat plasma sample were determined by enzymatic assays. When NYS and liposomal NYS were incubated in human, dog, or rat plasma, the majority of the NYS was recovered in the LPDP fraction. For the 5- and 60-min incubation times for all plasmas measured, a significantly greater percentage of NYS was recovered in the lipoprotein fraction (primarily HDL) following the incubation of liposomal NYS than following the incubation of NYS. There was a significant correlation between the lipoprotein lipid and protein profiles in human, dog, and rat plasmas and the distribution of NYS and liposomal NYS in plasma. In particular, differences in the proportion of plasma lipoprotein cholesterol, triglyceride, and apolar lipids (cholesteryl ester and triglycerides) carried by HDL influenced the distribution of NYS and liposomal NYS within plasmas of different species. These findings suggest that the distribution of NYS among plasma lipoproteins of different species is defined by the proportion of lipid carried by HDL, and this is possibly an important consideration when evaluating the pharmacokinetics, toxicities, and activities of these compounds following administration to different animal species.
机译：这项研究的目的是对血浆中游离制霉菌素（NYS）和脂质体NYS（Nyotran）分布的种间比较。将浓度为5、10和20μgNYS / ml的NYS和脂质体NYS在人，狗和大鼠血浆中于37°C孵育5、60和180分钟。在这些孵育之后，通过密度梯度超速离心将血浆样品分离为它们的高密度脂蛋白（HDL），富含甘油三酸酯的脂蛋白，低密度脂蛋白和缺乏脂蛋白的血浆（LPDP）馏分，并对每个馏分进行NYS分析通过高压液相色谱法。通过酶测定法测定每个人，狗或大鼠血浆样品中的总血浆和脂蛋白胆固醇，甘油三酸酯和蛋白质浓度。当将NYS和脂质体NYS在人，狗或大鼠血浆中孵育时，大部分NYS可以从LPDP馏分中回收。对于所有测得血浆的5分钟和60分钟孵育时间，脂质体NYS孵育后脂蛋白组分（主要是HDL）中回收的NYS百分比显着高于NYS孵育后。人，狗和大鼠血浆中的脂蛋白脂质和蛋白质谱与血浆中NYS和脂质体NYS的分布之间存在显着相关性。特别是，HDL携带的血浆脂蛋白胆固醇，甘油三酸酯和非极性脂质（胆固醇酯和甘油三酸酯）的比例差异会影响不同物种血浆中NYS和脂质体NYS的分布。这些发现表明，不同种类的血浆脂蛋白之间的NYS分布是由HDL携带的脂质的比例决定的，这可能是在评估这些化合物对不同动物种类给药后的药代动力学，毒性和活性时的重要考虑因素。 。

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