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.

在血管内注射后24小时内，对从白色念珠菌中纯化的D1I标记的(1*3)-β-D-葡聚糖的药代动力学、生物效应以及在血液和器官中的分布进行了分析。低剂量组中 β-葡聚糖的半衰期 (T<@D21/2@>D2alpha) 为 1.8 分钟高剂量组（9.3mug/kg）和1.4分钟（222mug/kg），全身清除率分别为1.12（]SY.+-.[）0.30和1.17（]SY.+-.[）0.16（ ml/min，平均值 (]SY.+-.[) SD)，还分别对 (1*3)-β-D-葡聚糖的血清浓度进行了生物学测定。通过使用日本鲎的凝血因子 G 进行的测试（G 测试），通过生物学和同位素测量，β-葡聚糖浓度之间存在良好的相关性，但在最初 2 小时内，生物活性下降得更快； 3-24 小时期间 β-葡聚糖的同位素浓度在 24 小时的观察期间，兔子状况良好，β-葡聚糖未能改变血细胞计数、TNF 水平和与细胞区室相关的<@D1125@>D1I-β-葡聚糖最初低于3%（大部分在血小板中），并在接下来的2小时内进一步下降（p=0.0001）。 <@D1125@>D1I-β-葡聚糖与无细胞血浆相关，血浆中的大部分似乎以未结合的形式存在，即不存在在所分析的六个主要器官中检测到的<@D1125@>D1I-β-葡聚糖在肝脏中含量超过80%。