may contribute to formation of the potentially toxic covalent zomepirac–
protein adductsin vitroin rat hepatocytes andin vivoin rats (Olsen et al., 2005).
The techniques described in this chapter can be of use to the optimization of
lead compounds during drug discovery processes. However, the link between
drug–protein adduct formation and toxicity has not been well defined.
Additional considerations should be taken, such as therapeutic area and
clinical doses. It has been suggested that a 10 mg daily dose rarely results in
drug-related adverse effects (Uetrecht, 1999). Thus, the propensity of
bioactivation should only be considered as one of the factors in the selection
of developmental drug candidates.
Acknowledgments
ZZ thanks Ying Li, Jason Ngui, and Qing Chen for their contributions to the
protocol development and to example presentations. JG thanks Qinling Qu for
his contribution to example presentations. The authors also thank Dr. Wei
Tang for critical review of the manuscript.
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