PT  - JOURNAL ARTICLE
AU  - Amita Datta-Mannan
TI  - Mechanisms Influencing The Disposition Of Monoclonal Antibodies And Peptides
AID  - 10.1124/dmd.119.086488
DP  - 2019 Jan 01
TA  - Drug Metabolism and Disposition
PG  - dmd.119.086488
4099  - http://dmd.aspetjournals.org/content/early/2019/05/01/dmd.119.086488.short
4100  - http://dmd.aspetjournals.org/content/early/2019/05/01/dmd.119.086488.full
AB  - Monoclonal antibodies (mAbs) and peptides are an important class of therapeutic modalities that have brought improved health outcomes in areas with limited therapeutic optionality. Presently, there more than 60 mAb and peptide therapeutics on the United States market, with over 450 more in various clinical stages of development in a broad array of therapeutic areas, including diabetes, auto-immune disorders, oncology, neuroscience, cardiovascular and infectious diseases. Notwithstanding this potential, there is high rate clinical rate of attrition, with approximately 10% reaching patients. A major contributor to the failure of the molecules is often times an incomplete or poor understanding of the pharmacokinetic and disposition profiles leading to limited or diminished efficacy. Increased and thorough characterization efforts directed at disseminating mechanisms influencing the pharmacokinetics and disposition of mAbs and peptides can aid in improving the design for their intended pharmacological activity and thereby, their clinical success. The pharmacokinetics and disposition factors for mAbs and peptides are broadly influenced by target-mediated drug disposition and non-target-related clearance mechanisms related to the interplay between the relationship of the structure and physiochemical properties of mAbs and peptides with physiological processes. This review focuses on non-target related factors influencing the disposition and PK of mAbs and peptides. Contemporary considerations around the increasing in silico approaches to identify non-target related molecule limitations and enhancing the druggability of mAbs and peptides, including parenteral and non-parenteral delivery strategies that are geared towards improving patient experience and compliance, are also discussed.SIGNIFICANCE STATEMENT n/a