Gordon M, Guralnik M, Kaneko Y, Mimura T, Goodgame J, Lang W
Aji Pharma USA, Inc., Glenpointe Centre West, Teaneck, NJ 07666, USA.
J Med. 1995;26(3-4):97-131.
Curdlan sulfate (CRDS) is a semi-synthetic sulfated polysaccharide which inhibits the attachment of HIV to T-cells, and also has intracellular anti-HIV activity. In Phase I clinical trials, CRDS was found in 4 hr i.v. infusions, to be well tolerated up to 200 mg/70 kg and unexpectedly to produce marked, dose-related increases in CD4 lymphocytes in HIV-infected patients. Prolongation of bleeding time is expected to be the dose limiting toxicity, but no episodes of bleeding were seen. In one of the studies in this report, CRDS was administered i.v. daily for 7 days to HIV patients at doses of 40, 100, 140 and 180 mg/70 kg/day. At the higher doses, marked increases in CD4 and CD8 lymphocytes were observed. These increases mainly returned to baseline after 24 hr. To further delineate the pharmacokinetics of these changes in CD4 and CD8 lymphocytes, another Phase I study was done in which CRDS was infused i.v. over a 30 min period in HIV patients at single doses of 25, 50, 75, 100, 125, 150, 175 and 200 mg/70 kg/day. The drug was well tolerated in all cases and marked increases in CD4 lymphocytes were again seen at the higher doses, in some cases amounting to increases of 500 cells/mm3 after a single dose. The half-life of CRDS in man was found to be about two hours, as measured by activated partial thromboplastin time (APTT) and by plasma assays.
硫酸凝结多糖（CRDS）是一种半合成硫酸化多糖，它能抑制HIV与T细胞的附着，还具有细胞内抗HIV活性。在I期临床试验中，发现静脉输注4小时的CRDS，在剂量高达200mg/70kg时耐受性良好，并且出乎意料地使HIV感染患者的CD4淋巴细胞显著增加，且与剂量相关。预计出血时间延长是剂量限制性毒性，但未观察到出血事件。在本报告的一项研究中，以40、100、140和180mg/70kg/天的剂量，对HIV患者每天静脉注射CRDS，持续7天。在较高剂量下，观察到CD4和CD8淋巴细胞显著增加。这些增加在24小时后主要恢复到基线水平。为了进一步描述CD4和CD8淋巴细胞这些变化的药代动力学，进行了另一项I期研究，在HIV患者中，以25、50、75、100、125、150、175和200mg/70kg/天的单次剂量，在30分钟内静脉输注CRDS。在所有情况下，该药物耐受性良好，在较高剂量下再次观察到CD4淋巴细胞显著增加，在某些情况下，单次给药后增加量达500个细胞/mm³。通过活化部分凝血活酶时间（APTT）和血浆检测测得，CRDS在人体内的半衰期约为两小时。
