Fig. 2
From: A Fab of trastuzumab to treat HER2 overexpressing breast cancer brain metastases
Pharmacokinetic studies after intra-CSF administration of anti-HER2 antibodies in rats. (A-B) Pharmacokinetic study with a total dose of 36.5 µg administered for each antibody (N = 4 rats for trastuzumab, N = 6 rats for Fab#2), in the CSF (A) and in the serum (B). (C-D) Pharmacokinetic study with a total dose of 1400 µg administered for each antibody (N = 4 rats for trastuzumab, N = 3 rats for Fab#2), in the CSF (C) and in the serum (D). (E) CSF-to-blood efflux for trastuzumab and anti-HER2 Fab#2 obtained on pooled data (N = 8 rats for trastuzumab and 9 rats for Fab#2). (F) Schematic of the population pharmacokinetic model used to describe concentrations of each antibody after administration in the cisterna magna. V1: volume of distribution of the CSF compartment, V2: volume of distribution of the serum compartment, k10: diffusion constant from CSF to brain; k12: diffusion constant from CSF to blood; k20: elimination from serum constant. (G) Brain concentration assessment of anti-HER2 Fab#2 and trastuzumab from 0 to 4 h after intra-CSF administration. Kpu, ubrain0−4 h = AUCu,brain0−4 h /AUCu,csf0−4 h. (H) Schematic dissection of rat brains. CE1 represents deeper brain area, including basal ganglia. CE2 represents posterior area including cerebellum and brainstem. CE3 represents cortical area