Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. II. Pharmacokinetics and immune response.
Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. II. Pharmacokinetics and immune response.
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多次大剂量鼠单克隆抗体CO17-1A的I期试验。
DOI：
10.1093/jnci/80.12.937
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
LoBuglio,AF
中科院分区：
文献类型：
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作者：
Khazaeli,MB;Saleh,MN;Wheeler,RH;Huster,WJ;Holden,H;Carrano,R;LoBuglio,AF
25例转移性胃肠道腺癌患者接受1 - 4次大剂量（400 mg）鼠单克隆抗体CO 17 -1A（17-1A）输注。第一次、第二次、第三次或第四次输注时17-1A的药代动力学无统计学差异;血浆半衰期分别为15.0 ± 1.7小时（n= 5）、15.1 ± 1.8小时（n= 10）、25.3 ± 6.2小时（n= 3）和14.4 ± 1.8小时（n= 5）。大多数患者对17-1A有抗体应答，在输注后15-22天达到峰值水平。在第二次或第三次输注时，17-1A血清抗体的存在并未显著改变该大剂量抗体的药代动力学。25名患者中有4名未能产生抗体应答，但这与17-1A的给药量无关。在1周内给予4剂400 mg，连续提供循环17-1A 10天。[J Natl Cancer Inst 1988; 80：937-942]
Twenty-five patients with metastatic gastrointestinal adenocarcinoma received one to four infusions of large doses (400 mg) of murine monoclonal antibody CO17-1A (17-1A). The pharmacokinetics of 17-1A at the time of first, second, third, or fourth infusion were not statistically different; plasma half-lives were 15.0 ± 1.7 hours (n= 5), 15.1 ± 1.8 (n= 10), 25.3 ± 6.2 (n= 3), and 14.4 ± 1.8 (n= 5), respectively. Most patients had an antibody response to 17-1A, with peak levels occurring 15–22 days after infusion. The presence of serum antibody to 17-1A at the time of the second or third infusion did not significantly alter the pharmacokinetics of this large dose of antibody. Four of 25 patients failed to develop an antibody response, but this did not correlate with the amount of 17-1A administered. The administration of four doses of 400 mg over 1 week provided continuously circulating 17-1A for 10 days. [J Natl Cancer Inst 1988; 80: 937–942]