人血清白蛋白的相互作用亲电代谢物1-O-gemfibrozil-beta-D-glucuronide。
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公元前Sallustio仙童英航,Pannall公关
人血清白蛋白的相互作用亲电代谢物1-O-gemfibrozil-beta-D-glucuronide。
药物金属底座Dispos。1997年1月,25(1):则高达55 -。
- PubMed ID
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9010630 (在PubMed]
- 文摘
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葡糖苷酸酰基亲电代谢物是容易水解,进行分子内重排,内生蛋白质共价结合。二甲苯氧庚酸是广泛fibrate降脂剂代谢的葡糖苷酸酰基共轭人类。本研究的目的是检查1-O-gemfibrozil-beta-D-glucuronide与人血清白蛋白的相互作用。1-O-gemfibrozil-beta-D-glucuronide退化(大约200 microM)期间进行体外孵化项目在37摄氏度磷酸盐缓冲剂(pH值7.4或9.0),解决方案的人类血清白蛋白(pH值7.4),或新鲜人血浆(pH值7.4)。安定的影响、oxyphenbutazone和二甲苯氧庚酸1-O-gemfibrozil-beta-D-glucuronide退化,及其可逆结合白蛋白也进行了研究。飞行员在活体内研究两个病人志愿者管理1 g /天二甲苯氧庚酸。1-O-Gemfibrozil-beta-D-glucuronide不稳定,降解半衰期在4.1人力资源和44人力资源缓冲pH值9.0和7.4,分别;5.5和8.5人力资源和人力资源在人类血清白蛋白的pH值7.4解决方案或新鲜血浆,分别。退化是依赖于pH值和白蛋白的存在,似乎加快了分子内重排和共轭的水解。1-O-Gemfibrozil-beta-D-glucuronide高度可逆地绑定到白蛋白,平均的分数为0.028,其降解似乎与可逆结合的程度有关。 Hydrolysis and covalent binding were associated with the site II binding domain on albumin, because only diazepam inhibited these reactions. However, intramolecular rearrangement was increased when binding to the site I domain was inhibited. Covalent binding was also detected in vivo to human plasma proteins. The half-life of the gemfibrozil-protein adducts was 2.5-3 days. Albumin plays an important role in the disposition of acyl glucuronides by acting as: i) a transporter protein; ii) a potential catalyst for their degradation and, therefore, clearance; and iii) a target for covalent adduct formation.