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首页> 外文期刊>Journal of Pharmacy and Pharmaceutical Sciences >The Antiinflammatory Action and Pharmacokinetics of a Novel Glucosamine-based Di-Peptide Aminosugar
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The Antiinflammatory Action and Pharmacokinetics of a Novel Glucosamine-based Di-Peptide Aminosugar

机译：一种新型的基于氨基葡萄糖的二肽氨基糖的抗炎作用和药代动力学

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Purpose. We have previously shown favorable in vitro gut permeability for three novel di-peptide esters of glucosamine (GlcN) likely facilitated by the peptide transporter 1 (PepT1). Herein, we report the development of a novel assay for the determination of bioavailability of the peptide ester of interest, the anti-inflammatory properties of a glycine-valine ester derivative of GlcN (GVG) as well as its pharmacokinetics under healthy and inflammatory conditions. Methods. A pre-column derivatization (with 9-fluorenylmethoxycarbonyl) HPLC assay was developed to study bioavailability of GVG, GlcN or cleaved GlcN in the rats that were cannulated in their right jugular vein for blood collection. The compounds of interest were orally administered to both healthy and arthritic rats. Serial blood samples and urine were collected and assayed for the compounds. The stability of the GVG was also tested after incubation with the rat feces. Efficacy of GVG was tested in inflamed rats (injection of 0.2 mL of Mycobacterium butyricum in squalene) following GVG (20 and 30 mg/kg/day GlcN equivalent) or GlcN (20 and 90 mg/kg/day) administration. Arthritis index was calculated at the end of the experiment. Results. The assay was linear (ranged between 0.05-20 μg/mL) and reproducible (intra- and inter-day<10%). Among the tested compounds, only GVG showed a significantly higher plasma concentrations and urinary excretion than GlcN (≈3-fold increase). GVG showed a favorable stability in the rat feces. Adjuvant arthritis was completely prevented with doses greater than 20 mg/kg/day with GVG being 3-fold more potent than GlcN. Conclusion. The examined glycine-valine-GlcN di-peptide aminosugar is a potent anti-inflammatory compound due to its favorable properties to deliver GlcN into the systemic circulation. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
机译：目的。我们之前已经显示出了葡萄糖转运蛋白1（PepT1）可能促进的三种新型葡糖胺二肽酯（GlcN）的体外肠道通透性。在此，我们报告了一种新型测定方法的开发，该测定方法用于测定目标肽酯的生物利用度，GlcN的甘氨酸-缬氨酸酯衍生物（GVG）的抗炎特性以及在健康和炎性条件下的药代动力学。方法。开展了柱前衍生化（使用9-芴基甲氧基羰基）HPLC分析法，研究了在右颈静脉插管采血的大鼠中GVG，GlcN或裂解的GlcN的生物利用度。将目的化合物口服给予健康和关节炎大鼠。收集连续的血样和尿液并分析化合物。与大鼠粪便孵育后，还测试了GVG的稳定性。在施用GVG（相当于20和30 mg / kg /天，相当于GlcN）或GlcN（相当于20和90 mg / kg /天）后，在发炎的大鼠中（注射了0.2 mL丁酸分枝杆菌在角鲨烯中）测试了GVG的功效。在实验结束时计算关节炎指数。结果。该测定是线性的（范围在0.05-20μg/ mL之间）并且可重复（日内和日间<10％）。在测试的化合物中，只有GVG的血浆浓度和尿排泄量显着高于GlcN（增加了约3倍）。 GVG在大鼠粪便中显示出良好的稳定性。大于20 mg / kg / day的剂量可完全预防佐剂性关节炎，其中GVG的效力是GlcN的3倍。结论。所检查的甘氨酸-缬氨酸-GlcN二肽氨基糖是一种有效的抗炎化合物，因为它具有将GlcN输送至全身循环的良好特性。本文对发布后审查开放。已注册的读者（请参阅“针对读者”）可以通过在问题目录页面上单击摘要来发表评论。

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