Fig. 14
From: The need for mathematical modelling of spatial drug distribution within the brain
Example of a full physiologically-based pharmacokinetic drug distribution model of the CNS [143]. In this example model, the parameters for the plasma pharmacokinetic model are estimated (black) as input for the full model, while the parameters for the physiologically-based pharmacokinetic model are system-specific (blue) and drug-specific (green). Peripheral compartment 1 and 2 are used in cases where the plasma pharmacokinetic model requires an adequate description of drug concentration in the blood plasma. Here, brainmv: brain microvascular, CSFLV: CSF in the lateral ventricle, CSFTFV: CSF in the third and fourth ventricle, CSFCM: CSF in the cisterna magna, CSFSAS: CSF in the sub-arachnoid space, QCBF: cerebral blood flow, QtBBB: transcellular diffusion clearance at the BBB, QpBBB: paracellular diffusion clearance at the BBB, QtBCSFB1: transcellular diffusion clearance at the BCSFB, QpBCSFB1: paracellular diffusion clearance at the BCSFB1, QtBCSFB2: transcellular diffusion clearance at the BCSFB2, QpBCSFB2: paracellular diffusion clearance at the BCSFB2, QBCM: passive diffusion clearance at the brain cell membrane, QLYSO: passive diffusion clearance at the membrane of lysosomes, QECF: brain ECF flow, QCSF: CSF flow, AFin1-3: asymmetry factor into the CNS compartments 1-3, AFout1-3: asymmetry factor out from the CNS compartments 1-3, PHF1-7: pH-dependent factor 1-7, BF: binding factor. Image by [143] is licensed under CC BY 4.0