Figure 2.
Semi-PBPK model scheme (a) representing 99mTc–mebrofenin disposition in humans (Q denotes blood flow (ml/min), subscripts represent tissue or vascular compartments, as follows: liver (h), bile (bile), extrahepatic (“other”) tissue (o); clearance values are designated as CLuptake for influx from blood into tissue, CLefflux for efflux from tissue to blood, and CLbiliary for excretion from liver into bile). Simulations based on the semi-PBPK model and observed blood, liver, and bile curves for 99mTc–mebrofenin in subjects with quantitative scintigraphy data for (b) subject 8 (control), and (c) subject 17 (2 × 300 mg ritonavir). Circles represent observed blood samples, solid lines represent simulated blood concentrations, + symbols represent observed liver concentrations from attenuation-corrected (quantitative) scintigraphy data of the liver region of interest, dashed lines represent simulated liver concentrations, squares represent observed mass recovered in bile (corrected for gallbladder ejection fraction), and dotted lines represent simulated biliary excretion data. PBPK, physiologically based pharmacokinetic.