Physiologically Based Pharmacokinetic Modelling with Dynamic PET Data to Study the In Vivo Effects of Transporter Inhibition on Hepatobiliary Clearance in Mice

Figure 2

Model for the pharmacokinetic analysis. is the dose, and is the infusion duration (10 s). Initial for all compartments (indicated by black boxes) were zero. The parameters are mass transfer rate constants with the unit 1/time. The indices denote the source and target compartments, respectively (e.g., , for the mass transfer from blood plasma to hepatic compartment “Liver 1”). of peripheral tissue was best fit with two sets of rate constants for reversible transfer. The sum of the two plasma-to-tissue rate constants is . Several models were evaluated and the results were visually inspected. The shown model revealed reliable fits as concluded from the robust fit parameters and the visual inspection of the plotted fit functions. For [¹¹C]MT107 scans, (grey arrow) was set to 0. Tissue blood fractions ( multiplied with the organ or tissue volume and ) were added to the compartments where applicable. B, blood plasma; G, gallbladder plus intestine combined; H, liver; R, kidneys; T, peripheral tissue; U, urine.