PHARMACOKINETICS, SAFETY AND IMMUNOMODULATORY EFFECTS OF HUMAN RECOMBINANT INTERLEUKIN-1 RECEPTOR ANTAGONIST IN HEALTHY HUMANS
PHARMACOKINETICS, SAFETY AND IMMUNOMODULATORY EFFECTS OF HUMAN RECOMBINANT INTERLEUKIN-1 RECEPTOR ANTAGONIST IN HEALTHY HUMANS
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DOI：
10.1016/1043-4666(92)90078-6
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发表时间：
1992-09-01
期刊：
影响因子：
3.8
通讯作者：
DINARELLO, CA
中科院分区：
文献类型：
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作者：
GRANOWTIZ, EV;PORAT, R;DINARELLO, CA
人类重组白细胞介素-1受体拮抗剂（IL-1ra）的一期研究在18至30岁的健康男性中进行。25名志愿者接受单次连续3小时静脉输注剂量在1mg /kg至10mg /kg之间的IL-1ra。在给药3 h时，1 mg/kg和10 mg/kg剂量组血浆IL-1ra水平分别为3.1 μg/ml和29 μg/ml。输注后血浆IL-1ra水平迅速下降，初始半衰期为21分钟，终末半衰期为108分钟。在72小时内监测临床、血液学、生化、内分泌和免疫调节效应，并与4名接受生理盐水3小时输注的受试者进行比较。药物组和生理盐水组在症状、体格检查、全血细胞计数、单核细胞表型、血液化学谱、血清铁和血清皮质醇水平方面无临床显著差异。IL-1ra输注完成后获得的外周血单个核细胞（PBMC）体外合成的白细胞介素6明显少于盐水注射对照组的PBMC。这些数据表明，短暂阻断白细胞介素1受体是安全的，不会显著影响体内平衡。
A phase I study of human recombinant interleukin-1 receptor antagonist (IL-1ra) was conducted in healthy males between the ages of 18 and 30. Twenty-five volunteers received a single, 3 h continuous intravenous infusion of doses ranging between 1 mg/kg and 10 mg/kg IL-1ra. At 3 h into the infusion, plasma IL-1ra levels were 3.1 μg/ml and 29 μg/ml for the 1 mg/kg and 10 mg/kg doses, respectively. Post-infusion plasma IL-1ra levels declined rapidly, exhibiting an initial half-life of 21 min and a terminal half-life of 108 min. Clinical, hematological, biochemical, endocrinological and immunomodulatory effects were monitored over 72 h and compared to those of four subjects receiving a 3 h infusion of saline. There were no clinically significant differences between the drug and saline groups in symptoms, physical examinations, complete blood counts, mononuclear cell phenotypes, blood chemistry profiles, serum iron and serum cortisol levels. Peripheral blood mononuclear cells (PBMC) obtained after completion of the IL-1ra infusion synthesized significantly less interleukin 6 ex vivo than PBMC from saline-injected controls. These data suggest that transient blockade of interleukin 1 receptors is safe and does not significantly affect homeostasis.