Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 97, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2021.107703
Keywords
ICIs; Exposure-Response; Serum Concentration; Pharmacokinetics Parameters; Efficacy and Safety
Categories
Funding
- Youth Program of Clinical Pharmacy Research Foundation of Chinese Medical Association 2018 [320.6750.19090-42]
- Bethune.Medical Science Research Fund Project [B19404GT]
- General Program of Harbin Medical University Cancer Hospital Haiyan Fund [JJZD2021-25]
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This review examines the pharmacokinetics and pharmacodynamics of ICIs, factors influencing their safety and efficacy, exposure-response relationships, as well as concentration and time-dependent changes. Various covariates affecting exposure such as PK and PD characteristics, E-R relationships, and changes in drug concentration over time were explored to assess the efficacy and safety of ICIs.
Immune checkpoint inhibitors (ICIs) have been demonstrated an effective treatment in multiple tumor type, which restore the immune response to against cancer cell. Currently, approved ICIs include anti-cytotoxic Tlymphocyte antigen-4 (CTLA-4); anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) monoclonal antibodies (mAbs). In most these drugs, unique pharmacokinetic (PK) and pharmacodynamics (PD) have shown significant influence on clinical outcomes, which occurred by target-mediated drug concentration and time-varying drug clearance. An exposure-response (E-R) relationship has been used to describe the safety and efficacy of ICIs, and shown a plateaued E-R and time dependent changes in exposure. Using an enzyme linked immunosorbent assay (ELISA) or LC-MS/MS method to measure the peak concentration, trough concentration or area under the curve (AUC) of ICIs to assess the drug exposure. There are lots of covariates that have an influence on exposure, such as sex, clearance, body weight and tumor burden. In this review, we pooled data from studies of concentration or other pharmacokinetics parameter of mAbs to assess E-R in efficacy and safety.
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