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The in vivo CL was predicted from the scaled CL int by applying a parallel-tube blood-flow model that incorporates plasma protein binding and blood/plasma ratios (B/P) [16, 17], as described in the equation below: Allometric Scaling The CL and V ss of M8891 in human were estimated based on preclinical in vitro and in vivo PK data obtained in 4 species using allometric scaling approaches corrected for protein binding and CL int (CL-NAS fub , V-SA fub ) [18,19,20,21]

In contrast, effective translation of UA-driven mitophagy enhancement and EGT-mediated iron buffering will require integration of emerging mitochondrial biomarkers, such as lipid peroxidation signatures, mitophagy-related protein expression patterns, and iron-handling pathway indicators