Figure 2. Reverse Dosimetry Toxicodynamic IVIVE.

Equivalent external dose is determined by solving the TK model in reverse by deriving the external dose (that is, TK model input) that produces a specified internal concentration (that is, TK model output). Reverse dosimetry and IVIVE using HTTK relies on the linearity of the models. We calculate a scaling factor to relate in vitro concentrations (μM) to administered equivalent doses (AED). The scaling factor is the inverse of the steady state plasma concentration (C_ss) predicted for a 1 mg/kg/day exposure dose rate. We use Monte Carlo to simulate variability and propagate uncertainty to calculate an upper 95th percentile C_ss,95 for individuals who get higher plasma concentrations from the same exposure.