In Vitro Potency Correlated To In Vivo Pharmacodynamics

The correlation of in vitro potency and in vivo pharmacological (i.e., PD) response of Abs is one of the most widely pursued studies of its type for a number of reasons. Among the pharmacological properties we have examined,

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the observed potency at a suitable dose level is perhaps most closely associated with clinical efficacy, especially when appropriate in vivo models are chosen. However, one must recognize that the adjustment of dose levels can effectively overcome differences in potency to achieve similar efficacy. Many of the limitations previously mentioned for binding/targeting IVIVCs also apply to this situation; these include the influence of stroma or other connective tissues, the presence/absence of endogenous factors, and the influence of antigen shedding. Furthermore, variations in receptor expression levels, vascular permeability, interstitial pressure, and other parameters can also play a significant role. In general, efficacy related to cytotoxic effects or other pharmacological responses is a more complicated phenomenon than binding/targeting, typically requiring the successful interplay of a greater number of complex processes. As such, one must exercise caution in drawing conclusions from what may appear to be a relationship between in vitro and in vivo potency or efficacy.

In the present section, we have chosen to highlight Abs that recognize IgE, CD11a, CD20, CD30, CD40, HER2, fibroblast growth factor (FGF)19, tumor necrosis factor (TNF), and vascular endothelial growth factor (VEGF) to demonstrate the various methods used to develop IVIVC for therapeutic Abs in preclinical development.

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