Sampling Site Has a Critical Impact on Physiologically Based Pharmacokinetic Modeling.

摘要: It has been shown that arterial (central) and venous (peripheral) plasma drug concentrations can be very different. While pharmacokinetic studies typically measure from the peripheral vein such as arm vein, physiologically based (PBPK) models generally output simulated central compartment represents right atrium, a merge of superior inferior vena cava. In this study, forearm sampling site model was developed verified using nicotine, ketamine, lidocaine, fentanyl drugs. This allows meaningfully compared with observed data vein. The generalized effect PBPK on simulation investigated. Drugs metabolites large volumes distribution showed considerable concentration discrepancy between after intravenous or oral administration, resulting in significant differences values for Cmax time taken to reach (tmax) addition, metabolite profile an unexpected not Using compound, we show wrong lead biased evaluation subsequent erroneous parameter optimization. Such error parameters along discrepant could dramatically mislead prediction unstudied clinical scenarios, affecting assessment safety efficacy. Overall, study shows publications should specify sites match them those employed studies. SIGNIFICANCE STATEMENT Our (right atrium) during development gives rise parameterization when are collected clinically predictions concentration-time profiles scenarios. To address error, novel simulate applied different dosing