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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 7/2019

Open Access 01-07-2019 | Pharmacodynamics | Review Article

Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors

Authors: Maddalena Centanni, Dirk Jan A. R. Moes, Iñaki F. Trocóniz, Joseph Ciccolini, J. G. Coen van Hasselt

Published in: Clinical Pharmacokinetics | Issue 7/2019

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Abstract

Immune checkpoint inhibitors (ICIs) have demonstrated significant clinical impact in improving overall survival of several malignancies associated with poor outcomes; however, only 20–40% of patients will show long-lasting survival. Further clarification of factors related to treatment response can support improvements in clinical outcome and guide the development of novel immune checkpoint therapies. In this article, we have provided an overview of the pharmacokinetic (PK) aspects related to current ICIs, which include target-mediated drug disposition and time-varying drug clearance. In response to the variation in treatment exposure of ICIs and the significant healthcare costs associated with these agents, arguments for both dose individualization and generalization are provided. We address important issues related to the efficacy and safety, the pharmacodynamics (PD), of ICIs, including exposure–response relationships related to clinical outcome. The unique PK and PD aspects of ICIs give rise to issues of confounding and suboptimal surrogate endpoints that complicate interpretation of exposure–response analysis. Biomarkers to identify patients benefiting from treatment with ICIs have been brought forward. However, validated biomarkers to monitor treatment response are currently lacking.
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Metadata
Title
Clinical Pharmacokinetics and Pharmacodynamics of Immune Checkpoint Inhibitors
Authors
Maddalena Centanni
Dirk Jan A. R. Moes
Iñaki F. Trocóniz
Joseph Ciccolini
J. G. Coen van Hasselt
Publication date
01-07-2019
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 7/2019
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-019-00748-2

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Letter to the Editor

Comment on “Target-Controlled Continuous Infusion for Antibiotic Dosing: Proof-of-Principle in an In-silico Vancomycin Trial in Intensive Care Unit Patients”

Letter to the Editor

Authors’ Reply to Coste et al.: “Levothyrox® New and Old Formulations: Are they Switchable for Millions of Patients?”

Original Research Article

Population Pharmacokinetic Modeling of Benralizumab in Adult and Adolescent Patients with Asthma