Fig. 7. (A) Schematic of systems pharmacodynamic model linking methylprednisolone pharmacokinetics, glucocorticoid receptor dynamics, and hepatic mRNA and protein biomarkers to select efficacy and toxicity end-points in rats. Stimulation is denoted as open rectangles, and inhibition is denoted by closed rectangles. Heavy lines reflect turnover while broken lines reflect effects. (B) Measured and model-fitted profiles of steroid PK after 50 mg/kg i.v. (top-left) and i.m. (top-middle) doses, fitted profiles of receptor (mRNA, free cytosolic, and nuclear complex) dynamics (top right), TAT signaling pathway (middle row), and acute phase response and lymphocyte dynamics (bottom). Orange, PK; green, mRNA; blue, protein; and red, physiologic PD end-point. Figure adapted from Ayyar et al., 2018b with permission by Springer Nature.