异卵黄蛋白-2'-O-β-D-吡喃葡糖苷（IVG）在Sprague-Dawley大鼠体内的药代动力学和组织分布。

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current drug metabolism Pub Date : 2023-01-01 DOI:10.2174/0113892002263771230920092659

Xiaotong Zhao, Leilei Fang, Tan Yang, Yanqing Zhang, Junbo Xie

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引用次数: 0

摘要

背景：异卵黄蛋白-2“-O-D-吡喃葡糖苷（IVG）已知具有镇静和催眠作用。然而，对IVG的体内药代动力学和组织分布知之甚少，IVG和内标（IS）显示强烈的负电离信号。MRM分析选择离子跃迁m/z 593.3→ 293.0（IVG）和m/z 579.8→ 271.4（IS）。方法验证表明具有高精密度、准确度和可靠性，定量限低于20 ng/mL。静脉注射5.0 mg/kg IVG后，观察到大鼠血浆快速清除，半衰期（t1/2）为3.49±0.99 h，清除率为54.53±11.90 mL/kg/h。曲线下面积（AUC0-12h）为37.79±7.65µg·h/mL，表明代谢率较高。在评估组织分布时，肝脏（30.32±3.06µg/g）的积聚量最高，其次是肾脏（20.58±2.12µg/g，）和肠道（6.69±0.93µg/g），这表明IVG倾向于集中在这些组织中。重要的是，IVG在大脑中的存在突出了其穿越血脑屏障的潜力。这些发现表明，静脉注射后，IVG迅速而广泛地分布在各种大鼠组织中。结论：本研究为IVG的药代动力学和组织分布提供了有价值的信息，表明它有可能成为一种新的、有效的镇静和抗焦虑治疗药物。

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Pharmacokinetics and Tissue Distribution of Isovitexin-2''-O-β-D-glucopyranoside (IVG) in Sprague-Dawley Rats.

Background: Isovitexin-2"-O-D-glucopyranoside (IVG) has been known to exhibit sedative and hypnotic effects. However, there is little understanding of the in vivo pharmacokinetics and tissue distribution of IVG.

Objective: This study aimed to investigate the pharmacokinetics and tissue distribution of IVG.

Methods: The study employed an HPLC-ESI-MS/MS method to analyze the pharmacokinetics and tissue distribution of IVG.

Results: Under mass spectrometry, IVG and internal standard (IS) showed strong negative ionization signals. MRM analysis chose ion transitions m/z 593.3 → 293.0 (IVG) and m/z 579.8 → 271.4 (IS). Method validation indicated high precision, accuracy, and reliability with a quantitation limit under 20 ng/mL. After intravenously administering 5.0 mg/kg of IVG, rapid clearance from rat plasma was observed, with a half-life (t_1/2) of 3.49 ± 0.99 h and a clearance rate of 54.53 ± 11.90 mL/kg/h. The area under the curve (AUC_0-12h) of 37.79 ± 7.65 μg·h/mL indicated a brisk metabolic rate. Evaluating the tissue distribution, the highest accumulation was seen in the liver (30.32 ± 3.06 μg/g), followed by the kidney (20.58 ± 2.12 μg/g) and intestine (6.69 ± 0.93 μg/g), suggesting a propensity for IVG to concentrate in these tissues. Importantly, the presence of IVG in the brain underlines its potential to traverse the blood-brain barrier. These findings revealed that following intravenous administration, IVG was swiftly and broadly distributed throughout various rat tissues.

Conclusion: This study provides valuable information on the pharmacokinetics and tissue distribution of IVG, implicating its potential as a novel and effective drug candidate for sedative and anxiolytic treatment.

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来源期刊

Current drug metabolism 医学-生化与分子生物学

CiteScore

4.30

自引率

4.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism, pharmacokinetics, and drug disposition. The journal serves as an international forum for the publication of full-length/mini review, research articles and guest edited issues in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the most important developments. The journal covers the following general topic areas: pharmaceutics, pharmacokinetics, toxicology, and most importantly drug metabolism. More specifically, in vitro and in vivo drug metabolism of phase I and phase II enzymes or metabolic pathways; drug-drug interactions and enzyme kinetics; pharmacokinetics, pharmacokinetic-pharmacodynamic modeling, and toxicokinetics; interspecies differences in metabolism or pharmacokinetics, species scaling and extrapolations; drug transporters; target organ toxicity and interindividual variability in drug exposure-response; extrahepatic metabolism; bioactivation, reactive metabolites, and developments for the identification of drug metabolites. Preclinical and clinical reviews describing the drug metabolism and pharmacokinetics of marketed drugs or drug classes.