Pharmacokinetics, biological effects and distribution of (1*3)-beta-D-glucan

(1*3)-β-D-葡聚糖的药代动力学、生物效应和分布

基本信息

批准号：
08670528
负责人：
YOSHIDA Minoru
金额：
$ 1.22万
依托单位：
Teikyo University school of Medicine (1997)Jichi Medical University (1996)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

The pharmacokinetics, biological effects and distribution in blood and organs of <@D1125@>D1I-labeled (1*3)-beta-D-glucan purified from Candida albicans were analyzed in rabbits during the 24 hr period following its I.V.administration. The intravascular half-life (T<@D21/2@>D2alpha) of beta-glucan was 1.8 min in the low dose group (9.3mug/kg) and 1.4 min in the high dose group (222mug/kg), and the total body clearance was 1.12 (]SY.+-。[) 0.30 and 1.17 (]SY.+-。[) 0.16 (ml/min, mean (]SY.+-。[) SD), respectively. The serum concentration of (1*3)-beta-D-glucan was also biologically determined by a test using coagulation factor G of the Japanese horseshoe crab (G Test). There was a good correlation between the concentration of beta-glucan, measured biologically and isotopically, during the initial 2 hr period ; however, biological activity then decreased faster than the isotopic concentration of beta-glucan during the 3-24 hr period. During the 24 hr period of observation, the rabbits remained well and beta-glucan failed to alter blood cell counts, TNF levels, and lipid metabolism. <@D1125@>D1I-beta-glucan associated with the cellular compartment initially was less than 3% (the majority in the platelets), and decreased further during the following 2 hr period (p=0.0001). Over 97% of <@D1125@>D1I-beta-glucan was associated with the cell-free plasma and the majority in plasma appeared to be present in unbound form, i.e., not associated with lipoproteins or plasma proteins. The liver contained more than 80% of the <@D1125@>D1I-beta-glucan detected in the six major organs analyzed.

在I.V.Adminmination I.V.Adminminitation之后的24小时，在24小时的兔子中分析了<@d1125@> d1i标记的血液和器官的药代动力学，生物学作用和分布。低剂量组（9.3mug/kg）（9.3mug/kg）的血管内半衰期（T <@D21/2@> d2alpha）为1.8分钟，高剂量组（222mug/kg）（222mug/kg）为1.4分钟，总身体清除率为1.12（SY.12（SY.11。SY。+ - 。+ - 。[）0.30和1.1.1.1.1.1.1.1.1.1.10（]）（]（Min）。（]sy。+ - 。[）sd）。（1*3）-beta-d-glucan的血清浓度也通过使用日本马蹄蟹（G检验）的凝结因子G进行生物学确定。在最初的2个小时期间，在生物学和同位素上测量的β-葡聚糖的浓度之间存在良好的相关性。然而，在3-24小时期间，生物学活性的提高比β-葡聚糖的同位素浓度更快。在观察的24小时期间，兔子保持良好，β-葡聚糖未能改变血细胞计数，TNF水平和脂质代谢。 <@d1125@>与细胞室相关的D1I-BETA葡萄糖最初小于3％（血小板中的大多数），在接下来的2小时期间进一步增加（P = 0.0001）。超过97％的<@d1125@> d1i-beta-葡聚糖与无细胞血浆有关，并且血浆中的大多数似乎以未结合形式存在，即与脂蛋白或血浆蛋白无关。肝脏中含有超过80％的<@d1125@> d1i-beta-glucan在所分析的六个主要器官中检测到的。