Abstract:
:The development of multiple drug modalities over the past 20 years has dramatically expanded the therapeutic space for intervention in disease processes. Rather than being alternative therapeutic approaches, these modalities tend to be complimentary both in the scope of target space and the biological mechanisms harnessed for disease control. Realization of these therapeutic opportunities requires an understanding of the physiological, biochemical and biological barriers that control exposure to the drug target and resulting biological response. Consequently, successful application of ADME and PK/PD to characterization of novel therapeutics needs to consider the unique attributes conferred by the therapeutic modality and the desired and potential off-target biological responses. The discussion that follows provides examples of how barriers to exposure, and translation of exposure to efficacy can change across different modalities. Additionally, recommendations are made for ADME analysis in which biological barriers and mechanistic properties unique to specific modalities are used to focus ADME PK optimization and characterization.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Hochman JHdoi
10.1016/j.xphs.2020.09.057subject
Has Abstractpub_date
2021-01-01 00:00:00pages
35-41issue
1eissn
0022-3549issn
1520-6017pii
S0022-3549(20)30599-2journal_volume
110pub_type
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