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Current Drug Metabolism

Author(s): Xiaotong Zhao, Leilei Fang, Tan Yang, Yanqing Zhang* and Junbo Xie*

DOI: 10.2174/0113892002263771230920092659

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

Page: [656 - 666] Pages: 11

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Abstract

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 (t1/2) of 3.49 ± 0.99 h and a clearance rate of 54.53 ± 11.90 mL/kg/h. The area under the curve (AUC0-12h) 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.

Keywords: Ziziphus jujube seed, isovitexin-2''-O-β-D-glucopyranoside, HPLC-ESI-MS/MS, pharmacokinetics, tissue distribution, sedative.

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