PNNL

Abstract

Provisional advisory levels (PALs) are tiered exposure limits for toxic chemicals in air and drinking water that are developed to assist in emergency responses. Physiologically-based pharmacokinetic (PBPK) modeling can support this process by enabling extrapolations across doses, and exposure routes, thereby addressing gaps in the available toxicity data. Here, we describe the development of a PBPK model for Fentanyl – a synthetic opioid used clinically for pain management – to support the establishment of PALs. Starting from an existing model for intravenous Fentanyl, we first optimized distribution and clearance parameters using several additional IV datasets. We then calibrated the model for oral and inhalation exposures using pharmacokinetic datasets for various Fentanyl formulations. Predictions of the calibrated model were in good agreement with the >50 datasets considered here. For aerosolized pulmonary Fentanyl, F=1 and t90