Antibody-Drug Conjugates: Pharmacokinetic/Pharmacodynamic Modeling, Preclinical Characterization, Clinical Studies,
William D Hedrich1, Tamer E Fandy2, Hossam M Ashour3,4
1Pharmacokinetics and Biopharmaceutics Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Rm. N525, 20 N. Pine St., Baltimore, MD, 21201, USA.
Abstract:
Antibody-drug conjugates are an emerging class of biopharmaceuticals changing the landscape of targeted chemotherapy. These conjugates combine the target specificity of monoclonal antibodies with the anti-cancer activity of small-molecule therapeutics. Several antibody-drug conjugates have received approval for the treatment of various types of cancer including gemtuzumab ozogamicin (Mylotarg®), brentuximab vedotin (Adcetris®), trastuzumab emtansine (Kadcyla®), and inotuzumab ozogamicin, which recently received approval (Besponsa®). In addition to these approved therapies, there are many antibody-drug conjugates in the drug development pipeline and in clinical trials, although these fall outside the scope of this article. Understanding the pharmacokinetics and pharmacodynamics of antibody-drug conjugates and the development of pharmacokinetic/pharmacodynamic models is indispensable, albeit challenging as there are many parameters to incorporate including the disposition of the intact antibody-drug conjugate complex, the antibody, and the drug agents following their dissociation in the body. In this review, we discuss how antibody-drug conjugates progressed over time, the challenges in their development, and how our understanding of their pharmacokinetics/pharmacodynamics led to greater strides towards successful targeted therapy programs.
More Related Videos
Related Concept Videos
Pharmacokinetic–Pharmacodynamic Relationship: Model Components
Pharmacodynamic Models: Overview
Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions
Pharmacokinetic–Pharmacodynamic Relationship: Problems
Pharmacokinetic–Pharmacodynamic Relationship: Exposure, Response and Effect
Preclinical Development: Overview


