Pharmacokinetics and Pharmacodynamics of Antibody-Drug Conjugates Administered via Subcutaneous and Intratumoral Routes

药代动力学 药效学 药理学 加药 医学 治疗指标 曲妥珠单抗 体内 抗体-药物偶联物 毒性 结合 药品 抗体 癌症 单克隆抗体 内科学 免疫学 生物技术 数学分析 乳腺癌 生物 数学
作者
Hsuan Ping Chang,Huyen Khanh Le,Dhaval K. Shah
出处
期刊:Pharmaceutics [Multidisciplinary Digital Publishing Institute]
卷期号:15 (4): 1132-1132 被引量:12
标识
DOI:10.3390/pharmaceutics15041132
摘要

We hypothesize that different routes of administration may lead to altered pharmacokinetics/pharmacodynamics (PK/PD) behavior of antibody-drug conjugates (ADCs) and may help to improve their therapeutic index. To evaluate this hypothesis, here we performed PK/PD evaluation for an ADC administered via subcutaneous (SC) and intratumoral (IT) routes. Trastuzumab-vc-MMAE was used as the model ADC, and NCI-N87 tumor-bearing xenografts were used as the animal model. The PK of multiple ADC analytes in plasma and tumors, and the in vivo efficacy of ADC, after IV, SC, and IT administration were evaluated. A semi-mechanistic PK/PD model was developed to characterize all the PK/PD data simultaneously. In addition, local toxicity of SC-administered ADC was investigated in immunocompetent and immunodeficient mice. Intratumoral administration was found to significantly increase tumor exposure and anti-tumor activity of ADC. The PK/PD model suggested that the IT route may provide the same efficacy as the IV route at an increased dosing interval and reduced dose level. SC administration of ADC led to local toxicity and reduced efficacy, suggesting difficulty in switching from IV to SC route for some ADCs. As such, this manuscript provides unprecedented insight into the PK/PD behavior of ADCs after IT and SC administration and paves the way for clinical evaluation of these routes.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
G1997发布了新的文献求助10
刚刚
打打应助闫雪采纳,获得10
2秒前
2秒前
露亮发布了新的文献求助10
2秒前
peterlee发布了新的文献求助10
2秒前
congenialboy发布了新的文献求助10
3秒前
苏卿应助zys采纳,获得30
3秒前
科研助手6应助zys采纳,获得10
3秒前
清歌浊酒完成签到,获得积分20
4秒前
jay发布了新的文献求助10
5秒前
热情鹤发布了新的文献求助30
7秒前
香蕉觅云应助帅男采纳,获得30
7秒前
8秒前
11秒前
小二郎应助wenlin采纳,获得10
12秒前
星辰大海应助大喵采纳,获得10
14秒前
15秒前
16秒前
天天快乐应助xxxllllll采纳,获得30
16秒前
小马甲应助amai采纳,获得10
17秒前
17秒前
热情鹤完成签到,获得积分10
18秒前
方便面了吗完成签到,获得积分20
19秒前
19秒前
19秒前
李健的小迷弟应助llllhh采纳,获得10
20秒前
今夜有雨完成签到 ,获得积分10
21秒前
21秒前
21秒前
21秒前
wenlin发布了新的文献求助10
23秒前
王武聪关注了科研通微信公众号
24秒前
peterlee发布了新的文献求助10
25秒前
wish发布了新的文献求助10
25秒前
风清扬应助慈祥的水池采纳,获得50
27秒前
大喵发布了新的文献求助10
27秒前
30秒前
31秒前
32秒前
33秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3989797
求助须知:如何正确求助?哪些是违规求助? 3531914
关于积分的说明 11255516
捐赠科研通 3270597
什么是DOI,文献DOI怎么找? 1805008
邀请新用户注册赠送积分活动 882181
科研通“疑难数据库(出版商)”最低求助积分说明 809190