Absorption

吸收
  • 文章类型: Journal Article
    酸性气体在石油和天然气工业中的吸收由于其毒性和腐蚀作用而很重要。最近,各种研究人员已经研究了基于水性或有机溶剂的纳米流体作为吸收剂的应用。在这项研究中,利用基于Box-Behnken三级实验设计的响应面方法(RSM),利用单个鼓泡柱来研究水基纳米流体对SO2和CO2吸收过程的影响。考虑到这一点,CO2和SO2分别在充满纳米流体之一的泡罩塔的底部注入:Al2O3-水,SiO2-水,或ZnO-水为每个实验。然后,已经阐明了纳米流体中SO2或CO2的吸收速率。重要参数的影响,包括纳米颗粒的重量分数(NP)(0.01、0.055和0.1wt。%),气液接触时间(150、300和450s),研究了注气喷嘴的直径(0.46、0.57和0.68mm)。结果表明,在ZnO-水纳米流体中观察到两种气体的最大摩尔通量,其次是SiO2-水纳米流体。此外,增加纳米粒子的质量分数和气泡尺寸导致摩尔通量上升。然而,增加气体-液体接触时间导致所述气体的摩尔通量降低。最后,已经提出了一组准确的方程来预测在这项工作中评估的各种纳米流体中SO2和CO2的摩尔通量。
    The absorption of acidic gases in the oil and gas industries is important due to their toxicity and corrosive effects. Recently, the application of nanofluids based on aqueous or organic solvents as absorbents has been examined by a variety of researchers. In this study, a single bubble column was exploited to study the effect of water-based nanofluids on the absorption processes of SO2 and CO2 using response surface methodology (RSM) based on Box-Behnken three-level experiment design. With this in mind, CO2 and SO2 are separately injected at the bottom of a bubble column filled with one of the nanofluids: Al2O3-water, SiO2-water, or ZnO-water for each experiment. Then, the rate of SO2 or CO2 absorption in the nanofluids has been elucidated. The effect of important parameters including the weight fraction of the nanoparticles (NPs) (0.01, 0.055, and 0.1 wt.%), gas-liquid contact time (150, 300, and 450 s), and the diameter of nozzle for gas injection (0.46, 0.57, and 0.68 mm) have been studied. Results revealed that the maximum molar flux of both gases was observed in the ZnO-water nanofluid, followed by the SiO2-water nanofluid. In addition, increasing the nanoparticle mass fraction and the bubble size causes the molar flux to rise. However, increasing the gas-liquid contact time causes the molar flux of the mentioned gases to decrease. Finally, a set of the accurate equations has been proposed to predict the molar flux of SO2 and CO2 in the various nanofluids assessed in this work.
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  • 文章类型: Journal Article
    动态体外吸收系统和通过PBPK的机械吸收模型在预测人类口服吸收方面都显示出希望。尽管这些努力在很大程度上是分开的;这项工作旨在整合这些方法的知识来研究RET抑制剂的口服吸收,普雷替尼,具有BCSII类属性。Tiny-TIM(TIMB.V.,Weteringbrug,荷兰)是一种动态的体外模型,可以密切模拟人体胃和小肠的连续生理状况。在禁食条件下以200mg和400mg的剂量与普雷替尼一起进行Tiny-TIM运行。在SimcypV21(Certara,曼彻斯特,英国)。在Tiny-TIM系统中,Pralsetinib的禁食生物可及性在200mg时为63%,在400mg时为53%;在升高的胃pH下,观察到400mg时降低了16%。Tiny-TIM中小肠区室的最大普雷替尼溶解度直接告知过饱和/沉淀模型参数。PBPK模型预测了在200mg和400mg时吸收的相似分数,与观察到的普雷替尼暴露的剂量成比例增加一致。将动态体外系统与机械吸收模型相结合,为理解和预测具有挑战性的低溶解度化合物的人体吸收提供了一种有前途的方法。
    Dynamic in vitro absorption systems and mechanistic absorption modeling via PBPK have both shown promise in predicting human oral absorption, although these efforts have been largely separate; this work aimed to integrate knowledge from these approaches to investigate the oral absorption of a RET inhibitor, pralsetinib, with BCS Class II properties. Tiny-TIM (TIM B.V., Weteringbrug​, The Netherlands) is a dynamic in vitro model with close simulation of the successive physiological conditions of the human stomach and small intestine. Tiny-TIM runs with pralsetinib were performed at doses of 200 mg and 400 mg under fasting conditions. Mechanistic modeling of absorption was performed in Simcyp V21 (Certara, Manchester, UK). Pralsetinib fasted bioaccessibility in the Tiny-TIM system was 63% at 200 mg and 53% at 400 mg; a 16% reduction at 400 mg was observed under elevated gastric pH. Maximum pralsetinib solubility from the small intestinal compartment in Tiny-TIM directly informed the supersaturation/precipitation model parameters. The PBPK model predicted a similar fraction absorbed at 200 mg and 400 mg, consistent with the dose proportional increases in observed pralsetinib exposure. Integrating dynamic in vitro systems with mechanistic absorption modeling provides a promising approach for understanding and predicting human absorption with challenging low solubility compounds.
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  • 文章类型: Journal Article
    跟进第一个PBPK模型,用于为α-生育酚构建的口服疫苗,本文探索了三种肽,以验证它们是否可以支持使用相同的PBPK建模方法作为佐剂的口服疫苗制剂。进行了文献综述,以验证在过去的几十年中,哪些肽被用作佐剂。人们注意到已经使用了MDP衍生物,其中一种甚至被商业批准,并在肿瘤学中静脉内给药时用作佐剂。本研究的目的是为三种MDP肽(MDP本身,MTP-PE,和murabutide),并验证它们是否可以作为口服疫苗的佐剂。考虑到肽在口服递送系统中面临的挑战,和改进配方,以实现更好的结果描述了一个逐步的方法,以达到最优化的模型。一旦模拟完成,比较结果以确定什么是作为口服佐剂的最佳肽。根据我们的结果,MTP-PE,目前批准和商业化的肽,可能有可能被纳入口服制剂。进行进一步的体内实验以确定当与适当的制剂口服施用时该肽的行为以克服口服递送系统的挑战将是令人感兴趣的。
    Following up on the first PBPK model for an oral vaccine built for alpha-tocopherol, three peptides are explored in this article to verify if they could support an oral vaccine formulation as adjuvants using the same PBPK modeling approach. A literature review was conducted to verify what peptides have been used as adjuvants in the last decades, and it was noticed that MDP derivatives have been used, with one of them even being commercially approved and used as an adjuvant when administered intravenously in oncology. The aim of this study was to build optimized models for three MDP peptides (MDP itself, MTP-PE, and murabutide) and to verify if they could act as adjuvants for an oral vaccine. Challenges faced by peptides in an oral delivery system are taken into consideration, and improvements to the formulations to achieve better results are described in a step-wise approach to reach the most-optimized model. Once simulations are performed, results are compared to determine what would be the best peptide to support as an oral adjuvant. According to our results, MTP-PE, the currently approved and commercialized peptide, could have potential to be incorporated into an oral formulation. It would be interesting to proceed with further in vivo experiments to determine the behavior of this peptide when administered orally with a proper formulation to overcome the challenges of oral delivery systems.
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  • 文章类型: Journal Article
    这项研究旨在评估手僵直对副交感神经紧张的影响,使用镇痛/伤害感受指数(ANI)和吸收的主观评分进行评估。解离,和健康志愿者的时间知觉。这是一项随机对照试验,包括法国医学催眠大会的参与者。90名志愿者被随机分为两组,所有人都接受了15分钟的积极催眠,有或没有手僵直症。通过ANI(镇痛/伤害感受指数)评估的相对副交感神经张力,在研究方案的不同时间记录心率和呼吸频率.催眠会话的实际持续时间,从闭眼到睁眼计算,也被记录下来。在催眠状态结束时,参与者在0-10量表上主观评估了他们的吸收和解离水平。他们还被要求估计从闭眼到睁眼的催眠时间。总的来说,90名受试者被纳入研究。由于方案标准的偏差,一名受试者被排除在外,留下89个主题进行分析。组间受试者特征相似。随着时间的推移,ANI的增加和心率和呼吸频率的降低具有统计学差异,无论有无手部僵直症,都没有差异。组间吸收和解离主观量表无统计学差异。催眠组和对照组之间的催眠疗程中位数[Q1-Q3]实际持续时间相似(9[8-10]分钟与8[7-10]分钟,分别)。然而,与对照组(10[5-10]min)相比,僵直症组的受试者估计催眠期持续时间(12[10-15]min)更长,平均±SD高估3±4min(p<0.001).催眠恍惚期间副交感神经舒适度增加,组间无差异。然而,在愉快的催眠状态下增加手部僵直症似乎并没有增加吸收或分离的感觉,而是在更长的一侧产生了时间失真,这在某些临床环境中可能有用。然而,还需要进一步的研究来更准确地确定催眠状态对手部僵直症的生理和心理影响。
    This study was designed to evaluate the effects on hand catalepsy on parasympathetic tone assessed using Analgesia/Nociception Index (ANI) and on subjective rating of absorption, dissociation, and time perception among healthy volunteers. This was a randomized controlled trial including participants to a medical hypnosis congress in France. Ninety volunteers were randomized in two arms, all receiving a fifteen-minute positive hypnotic trance, with or without hand catalepsy. The relative parasympathetic tone assessed by ANI (Analgesia/Nociception Index), heart rate and respiratory rate were recorded at different times of the study protocol. The actual duration of the hypnotic session, calculated from eye closing to eye opening, was also recorded. At the end of the hypnotic trance, participants subjectively rated their level of absorption and dissociation on a 0-10 scale. They were also asked to estimate the duration of the hypnotic session from eye closing to eye opening. In total, ninety subjects were included in the study. One subject was excluded because of deviation in the protocol standard, leaving eighty-nine subjects for analysis. Subject characteristics were similar between groups. There was a statistically different increase in ANI and decrease in both heart rate and respiratory rate over time with no difference with or without hand catalepsy. There was no statistically significant difference in absorption and dissociation subjective scales between groups. The median [Q1-Q3] actual duration of hypnotic sessions was similar between the catalepsy and the control groups (9 [8-10] min vs. 8 [7-10] min, respectively). However, subjects in the catalepsy group estimated a longer duration of the hypnotic session (12 [10-15] min) than in the control group (10 [5-10] min) with a mean ± SD overestimation of 3 ± 4 min (p < 0.001). Parasympathetic comfort increased during the hypnotic trance with no difference between groups. However, adding hand catalepsy to a pleasant hypnotic trance did not appear to increase feelings of absorption or dissociation but created time distortion on the longer side that could be useful in some clinical settings. Nevertheless, further study is still needed to determine more precisely the physiological and psychological effects on hand catalepsy during the hypnotic trance.
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  • 文章类型: Journal Article
    采用水热法制备了二硫化钼纳米花(MoS2NFs)。通过SEM对制备的MoS2NFs进行了表征,TEM,XRD,比表面积,拉曼和XPS。表征结果表明,花状球形MoS2由许多平均直径约300-400nm的超薄纳米片组成。MoS2NF还表现出优异的吸收和高荧光强度。为了探索MoS2NFs的生物学行为,通过UV-Vis吸收研究了MoS2NFs与牛血清白蛋白(BSA)的相互作用,荧光,同步荧光光谱,和循环伏安法。吸收和荧光结果表明,MoS2NFs和BSA通过形成复合物而强烈相互作用。Stern-Volmer常数和猝灭常数分别计算为约3.79×107Lmol-1和3.79×1015Lmol-1s-1。同步荧光表明复合物中的MoS2可能主要与BSA的色氨酸残基结合。循环伏安图表明,BSA的添加使MoS2NFs的电子还原比相应的自由状态更加困难。这些实验结果阐明了MoS2NFs通过与BSA结合在体内的有效运输和消除,并可以为评估MoS2NFs作为药物载体提供有用的指导。
    Molybdenum disulfide nanoflowers (MoS2 NFs) were prepared by hydrothermal method. The prepared MoS2 NFs was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), specific surface areas, Raman and X-ray photoelectron spectroscopy (XPS). The characterization results show that the flower-like spherical MoS2 is composed of many ultra-thin nanosheets with an average diameter of about 300-400 nm. MoS2 NFs also exhibits excellent UV-vis absorption and high fluorescence intensity. In order to explore the biological behavior of MoS2 NFs, the interaction between MoS2 NFs and bovine serum albumin (BSA) was studied by UV-Vis absorption, fluorescence, synchronous fluorescence spectra, and cyclic voltammetry. The results of absorption and fluorescence show that MoS2 NFs and BSA interact strongly through the formation of complexes in the ground state, and the static quenching is the main mechanism. The Stern-Volmer constant and the quenching constant was calculated about 3.79×107 L mol-1 and 3.79×1015 L mol-1 s-1, respectively. The synchronous fluorescence implied that MoS2 in the complex may mainly bind to tryptophan residues of BSA. The cyclic voltammograms indicated that the addition of BSA makes electron reduction of MoS2 NFs more difficult than the corresponding free state. The results show that hydrophobic forces play a major role in the binding interaction between BSA and MoS2 NFs.
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  • 文章类型: Journal Article
    与简单的溶出测定相比,双相溶出和同时溶出-渗透(D-P)系统都具有改善体外-体内相关性的巨大潜力。但是化验条件,并且评估方法仍需要完善,以便有效地将这些设备用于药物开发。因此,这项综合研究旨在比较小体积(16-20mL)D-P系统和小体积(40-80mL)双相溶出仪对5种含有市售药物的阿立哌唑(ARP)的生物等效性预测的准确性.测定条件,研究了特定的剂量依赖性以克服两种小规模系统的局限性。在双相溶解的情况下,随着ARP剂量的减少,体内最大血浆浓度(Cmax)的预测大大提高。而在D-P设置的情况下,整个片剂的使用给出了与缩放剂量一样准确的预测。使用剂量减少策略,两种设备都能够在Cmax比率的生物等效性预测中达到100%的准确性。在体内曲线下面积(AUC)预测的情况下,AUC比率的预测准确性不取决于剂量,两种仪器基于AUC结果预测生物等效性的准确率为100%。本文首次提出,不仅选择了通量测定的参数(如渗透率,初始通量,AUC值)用作机械模型(胃肠道统一理论)的输入参数以预测吸收率,但使用了整个体外通量曲线。在与体内数据比较期间,通过预测软件估计的所有部分吸收值落在+/-15%接受范围内。
    Both biphasic dissolution and simultaneous dissolution-permeation (D-P) systems have great potential to improve the in vitro-in vivo correlation compared to simple dissolution assays, but the assay conditions, and the evaluation methods still need to be refined in order to effectively use these apparatuses in drug development. Therefore, this comprehensive study aimed to compare the predictive accuracy of small-volume (16-20 mL) D-P system and small-volume (40-80 mL) biphasic dissolution apparatus in bioequivalence prediction of five aripiprazole (ARP) containing marketed drug products. Assay conditions, specifically dose dependence were studied to overcome the limitations of both small-scale systems. In case of biphasic dissolution the in vivo maximum plasma concentration (Cmax) prediction greatly improved with the dose reduction of ARP, while in case of the D-P setup the use of whole tablet gave just as accurate prediction as the scaled dose. With the dose reduction strategy both equipment was able to reach 100 % accuracy in bioequivalence prediction for Cmax ratio. In case of the in vivo area under the curve (AUC) prediction the predictive accuracy for the AUC ratio was not dependent on the dose, and both apparatus had a 100 % accuracy predicting bioequivalence based on AUC results. This paper presents for the first time that not only selected parameters of flux assays (like permeability, initial flux, AUC value) were used as an input parameter of a mechanistic model (gastrointestinal unified theory) to predict absorption rate but the whole in vitro flux profile was used. All fraction absorbed values estimated by Predictor Software fell within the ±15 % acceptance range during the comparison with the in vivo data.
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  • 文章类型: Journal Article
    在过去的三十年里,新型离子液体(IL)的合成及其在较新应用中的使用范围呈指数级增长。从这个令人眩晕的时期开始,众所周知,其中许多是吸湿的,在某些情况下,这限制了它们的使用或改变了它们测量的物理性质的值,并带来了所有的问题。在之前的一篇文章中,我们讨论了由ILs1-乙基-3-甲基咪唑氯化物获得的吸湿性等级,溴化1-乙基-3-甲基咪唑,甲基硫酸1-乙基-3-甲基咪唑,1-乙基-3-甲基咪唑鎓乙基硫酸酯,1-乙基-3-甲基吡啶鎓乙基硫酸酯,甲苯磺酸1-乙基-3-甲基咪唑,四氟硼酸1-乙基-3-甲基咪唑,四氟硼酸1-丁基-3-甲基咪唑,四氟硼酸1-十二烷基-3-甲基咪唑,四氟硼酸1-丁基-3-甲基吡啶,1-丁基-1-甲基哌啶双(三氟甲基磺酰基)酰亚胺,1-甲基-1-丙基吡咯烷鎓双(三氟甲基磺酰基)酰亚胺,1-丁基-1-甲基吡咯烷双(三氟甲基磺酰基)酰亚胺,和甲基三辛基铵双(三氟甲基磺酰基)酰亚胺。目的是确定化合物化学性质的影响,暴露的表面积,样品体积,激动,和温度。为此,我们将样品在大气室中暴露于相对湿度从15%突然增加到100%的几天,然后以温和的方式进行相反的过程。结果表明,水从大气中的吸附取决于IL的性质,尤其是阴离子,其中氯阴离子是特别重要的(氯化物烷基硫酸盐~溴化物>甲苯磺酸酯四氟硼酸盐)。对于EMIM-ES和EMIM-BF4样品也已证明,水分捕获的机理是吸收和吸附,暴露的表面积越小,单位面积水的质量比越高。
    Over the past three decades, the synthesis of new ionic liquids (ILs) and the expansion of their use in newer applications have grown exponentially. From the beginning of this vertiginous period, it was known that many of them were hygroscopic, which in some cases limited their use or altered the value of their measured physical properties with all the problems that this entails. In an earlier article, we addressed the hygroscopic grade achieved by the ILs 1-ethyl-3-methylimidazolium chloride, 1-ethyl-3-methylimidazolium bromide, 1-ethyl-3-methylimidazolium methyl sulfate, 1-ethyl-3-methylimidazolium ethyl sulfate, 1-ethyl-3-methylpyridinium ethyl sulfate, 1-ethyl-3-methylimidazolium tosylate, 1-ethyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylimidazolium tetrafluoroborate, 1-dodecyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylpyridinium tetrafluoroborate, 1-butyl-1-methylpiperidinium bis(trifluoromethyl sulfonyl)imide, 1-methyl-1-propylpyrrolidinium bis(trifluoromethyl sulfonyl)imide, 1-butyl-1-methylpyrrolidinium bis(trifluoromethyl sulfonyl)imide, and methyl trioctyl ammonium bis(trifluoromethyl sulfonyl)imide. The objective was to determine the influence of the chemical nature of the compounds, exposed surface area, sample volume, agitation, and temperature. For this purpose, we exposed the samples to abrupt increases in relative humidity from 15 to 100% for days in an atmosphere chamber and then proceeded with the reverse process in a gentle manner. The results show that the sorption of water from the atmosphere depends on the nature of the IL, especially the anion, with the chloride anion being of particular importance (chloride ≫ alkyl sulfates~bromide > tosylate ≫ tetrafluoroborate). It has also been proven for the EMIM-ES and EMIM-BF4 samples that the mechanism of moisture capture is both absorption and adsorption, and that the smaller the exposed surface area, the higher the ratio of the mass of water per unit area.
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  • 文章类型: Journal Article
    背景:工作场所的挑战会对员工和组织产生负面影响。弹性可以改善与工作相关的结果,如参与度,满意,和性能。在研究工作中的韧性方面存在差距,特别是在参与度和满意度方面。因此,这项研究旨在调查工作中的弹性,埃及石油和天然气公司工程师的工作投入和工作满意度。
    方法:这是一项横断面研究。目标人群是在埃及石油和天然气公司工作的工程师。这项研究是对100名工程师进行的。参与者通过在线问卷通过简单随机抽样技术进行登记。该研究于2023年5月至2023年9月底进行。数据是在2023年6月至8月期间收集的。数据是通过结构化和亲自完成的问卷获得的,通过电子邮件以电子方式传播。问卷包括个人信息,工作经验,由20个项目组成的工作弹性量表,乌得勒支工作敬业度量表,有九个项目来评估工作敬业度,并使用20项简式明尼苏达满意度问卷来确定员工满意度。双变量分析采用独立样本t检验和Mann-WhitneyU检验。通过Spearmanrho相关性测量得分之间的关联。使用简单线性和多元线性回归来预测工作投入和工作满意度。
    结果:在工作投入的所有方面观察到统计学上强的正相关,包括活力,吸收,和奉献精神。这项研究表明,韧性和工作投入之间存在显著相关性(r=0.356,p<0.05)。心理弹性与工作满意度有很强的相关性(r=0.608,p<0.05)。工作满意度和工作投入之间存在显著的中等相关性(r=0.396,p<0.05)。女性系数为-15.517的性别和系数为0.235的弹性都显着预测了工作投入。然而,工作满意度的重要预测因素是弹性(β=0.294),和工作参与度(β=0.283)。
    结论:弹性极大地影响工作投入和工作满意度。因此,组织需要提高员工的韧性,以创造积极的工作环境并提高生产率。
    BACKGROUND: Workplace challenges can negatively affect employees and the organization. Resilience improves work-related outcomes like engagement, satisfaction, and performance. Gaps exist in studying resilience at work, particularly in relation to engagement and satisfaction. Therefore, this study aims to investigate relationship between Resilience at Work, Work Engagement and Job Satisfaction among engineers in an Egyptian Oil and Gas Company.
    METHODS: It was a cross-sectional study. The target population was the engineers who are working in Egyptian Oil and Gas Company. The study was performed on 100 engineers. Participants were enrolled by simple random sampling technique via an online questionnaire. The study was conducted from May 2023 to the end of September 2023. The data were collected in the duration of June to August 2023. Data was obtained through a structured and personally accomplished questionnaire, which was disseminated electronically via email. The questionnaire comprises of personal information, work experience, a Resilience at Work scale consisting of 20 items, the Utrecht Work Engagement Scale with nine items to evaluate work engagement, and the 20-item Short-Form Minnesota Satisfaction Questionnaire was utilized to determine employee satisfaction. The bivariate analysis employed independent samples t-test and Mann-Whitney U test. The associations between scores were measured by Spearman rho correlation. Simple linear and multiple linear regressions were used to predict work engagement and job satisfaction.
    RESULTS: A statistically strong positive correlation was observed among all the aspects of work engagement, including vigor, absorption, and dedication. This study demonstrated a significant correlation between resilience and work engagement (r = 0.356, p < 0.05). There was a strong correlation between resilience and job satisfaction (r = 0.608, p < 0.05). A significant moderate correlation was determined between job satisfaction and work engagement (r = 0.396, p < 0.05). Both gender with a female coefficient of -15.517, and resilience with a coefficient of 0.235 significantly predicted work engagement. Whereas, the significant predictors of job satisfaction were resilience (β = 0.294), and work engagement (β = 0.283).
    CONCLUSIONS: Resilience greatly affects work engagement and job satisfaction. Thus, organizations need to promote resilience in employees to create a positive work environment and increase productivity.
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  • 文章类型: Randomized Controlled Trial
    通过微生物如酵母和/或益生菌的糖基化进行矿物质的生物转化产生与食物基质结合的营养素。导致生物利用度增加。这项研究的目的是比较与无机氧化锌相比,糖蛋白基质结合锌(GPM)对吸收的影响。16名参与者摄入11毫克锌作为GPM™无大豆锌(GPM,亚什兰,科尔尼,NJ,美国)或氧化锌(USP)。在0时采集血样(即,基线),摄入后30、60、90、120、180、240、300、360、420和480分钟。GPM锌浓度在120分钟时显著升高(p=0.02;12.4±5.1mcg/dL),180分钟(p=0.002;16.8±5.1mcg/dL),和240分钟(p=0.007;14.6±5.1mcg/dL),与USP氧化锌相比。此外,GPM锌显著增加iAUC40%(5840±2684vs.4183±1132mcg/dL*480分钟,p=0.02),与USP相比,GPM的Cmax值比USP高10%(148±21mcg/dL与135±17.5mcg/dL,p=0.08)。与USP相比,GPM的Tmax慢12%(112.5±38.7分钟与127.5±43.1分钟);然而,Tmax的差异没有达到统计学意义(p=0.28).与氧化锌相比,与糖蛋白基质结合的锌显着增加了吸收。
    Biotransformation of minerals via glycosylation by microorganisms such as yeast and/or probiotics yields nutrients bound to a food matrix, resulting in increased bioavailability. The purpose of this study was to compare the effects of glycoprotein matrix-bound zinc (GPM) on absorption compared to inorganic zinc oxide. Sixteen participants ingested 11 mg of zinc as either GPM™ Soy-Free Zinc (GPM, Ashland, Kearny, NJ, USA) or zinc oxide (USP). Blood samples were taken at 0 (i.e., baseline), 30, 60, 90, 120, 180, 240, 300, 360, 420, and 480 min post-ingestion. GPM zinc concentrations were significantly higher at 120 min (p = 0.02; 12.4 ± 5.1 mcg/dL), 180 min (p = 0.002; 16.8 ± 5.1 mcg/dL), and 240 min (p = 0.007; 14.6 ± 5.1 mcg/dL) in comparison to USP zinc oxide. In addition, GPM zinc significantly increased iAUC by 40% (5840 ± 2684 vs. 4183 ± 1132 mcg/dL * 480 min, p = 0.02), and Cmax values were 10% higher in GPM compared to USP (148 ± 21 mcg/dL vs. 135 ± 17.5 mcg/dL, p = 0.08). Tmax was 12% slower in GPM compared to USP (112.5 ± 38.7 min vs. 127.5 ± 43.1 min); however, differences in Tmax failed to reach statistical significance (p = 0.28). Zinc bound to a glycoprotein matrix significantly increased absorption compared to zinc oxide.
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  • 文章类型: Journal Article
    最近,驱虫药在解决各种疾病方面展示了多种治疗潜力,将它们定位为有希望的药物再利用候选人。然而,低生物利用度和缺乏坚实的药代动力学基础等挑战阻碍了成功的再利用。为了克服这些缺陷,我们旨在研究驱虫药的关键药代动力学因素,主要集中在吸收,分布,和代谢概况通过使用氯硝柳胺(NIC)作为模型药物。NIC的肠通透性受溶解度的影响很大,不能作为外排转运蛋白的底物。它显示了高的血浆蛋白结合。此外,代谢研究表明,通过广泛进行肠道葡萄糖醛酸化,NIC将具有较低的代谢稳定性。此外,我们以直接和时间依赖性方式研究了CYP介导的NIC药物-药物相互作用潜力.NIC对CYP1A2和CYP2C8显示出强烈的抑制作用,并且不太可能成为时间依赖性抑制剂。我们的发现可能有助于确定驱虫药的药代动力学中的基本因素,有可能促进他们的重新定位。
    Recently, anthelmintics have showcased versatile therapeutic potential in addressing various diseases, positioning them as promising candidates for drug repurposing. However, challenges such as low bioavailability and a lack of a solid pharmacokinetic basis impede successful repurposing. To overcome these flaws, we aimed to investigate the key pharmacokinetic factors of anthelmintics mainly focusing on the absorption, distribution, and metabolism profiles by employing niclosamide (NIC) as a model drug. The intestinal permeability of NIC is significantly influenced by solubility and doesn\'t function as a substrate for efflux transporters. It showed high plasma protein binding. Also, the metabolism study indicated that NIC would have low metabolic stability by extensively undergoing the intestinal glucuronidation. Additionally, we investigated the CYP-mediated drug-drug interaction potential of NIC in both direct and time-dependent ways. NIC showed strong inhibitory effects on CYP1A2 and CYP2C8 and is not likely to become a time-dependent inhibitor. Our findings could contribute to the identification of essential factors in the pharmacokinetics of anthelmintics, potentially facilitating their repositioning.
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