Fig. 3: Pharmacokinetic model to predict human tissue exposures for pretomanid.

a Schematic representation of the model for pretomanid tissue penetration based on a minimal physiology-based pharmacokinetic (mPBPK) framework. b Observed (black dots) and individual model-predicted (purple line) for 18F-pretomanid exposures in different tissues [brain, CSF (measured in cerebral ventricles), lung, and plasma (measured in left heart ventricle)] for the human subjects (S1–S8). Y-axis shows antibiotic exposure, and x-axis shows time (hours). CL = plasma clearance, Kp = partition coefficient for the tissue compartment, Qt = blood flow rate to tissue, Qlung = blood flow rate to lungs, Qbrain = blood flow rate to brain, QCSF = blood flow rate to brain ventricles (CSF), Rbrain = penetration ratio for brain, RCSF = penetration ratio for CSF, Rlung = penetration ratio for lungs.