Investigation of Inter-Individual Variability in Monoclonal Antibody Disposition

Substantial inter-individual variability (IIV) in monoclonal antibody (mAb) pharmacokinetics has been reported in the clinic. The sources of variability are not well understood and often not explored. Very few preclinical and clinical studies have attempted to examine the sources of IIV. Preclinical investigations, using appropriate mouse models, may allow detailed, mechanistic investigation of possible sources of IIV. The overall objective of this dissertation is to examine putative mechanistic determinants of mAb disposition, identify the sources of variability, elucidate the possible physiological mechanisms involved, and quantify their influence on mAb disposition. Overall, the work conducted in this dissertation evaluated possible sources of inter-subject and inter- antibody variability on mAb disposition. The mechanistic hypotheses tested within this dissertation improved our understanding of the physiological factors that contribute to variability in mAb pharmacokinetics. We anticipate that the mathematical models and biomarkers identified within this dissertation may be amenable to translation for further development and evaluation in clinical investigations, potentially leading toward the development of personalized mAb dosing regimens for patients.

Grantor dc:publisher

State University of New York at Buffalo

Year dc:date.issued

2018

Author dc:creator

• Thomas, Veena; 0000-0002-5202-6697

Contributors dc:contributor

• Balthasar, Joseph
• Pharmaceutical Sciences

• pharmaceutical sciences

Statement dc:rights

• Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.
• Copyright retained by author.

Language dc:language

eng

Handle dc:identifier

http://hdl.handle.net/10477/77924

OAI record oai:identifier

https://ubir.buffalo.edu/oai/request?verb=GetRecord&metadataPrefix=qdc&identifier=oai%3Aubir.buffalo.edu%3A10477%2F77924