Table II.

Parameter Estimates of the PBPK Model

Parameter			Value	RSE (%)
Estimates
CLE	Passive		83.3 mL/min	10.3
	+P-gp		52.7 mL/min	6.5
QPL-PER1	Passive		831 mL/min	9.6
QPL-PER2	Passive		93.5 mL/min	18.3
CLPL-Deep Brain	Passive		982 μL/min	14.7
	+P-gp		NAa
CLDeep Brain-PL	Passive		12.3 μL/min	19.8
	+P-gp	Resting period	228 μL/min	17.7
	+P-gp	Active period	659 μL/min	15.6
CLPL-ECF	Passive		25.7 μL/min	12.5
	+P-gp	Resting period	17 μL/min	18.5
	+P-gp	Active period	18.3 μL/min	18.5
CLECF-PL	Passive		4.63 μL/min	15.2
	+P-gp	Resting period	3.14 μL/min	36.3
	+P-gp	Active period	3.98 μL/min	48.0
CLPL-LV	Passive		3.23 μL/min	19.9
	+P-gp	Resting period	1.55 μL/min	30.1
	+P-gp	Active period	2.44 μL/min	17.5
CLLV-PL	Passive		0.513 μL/min	24.0
	+P-gp		NAa
CLPL-CM	Passive		0.753 μL/min	23.5
	+P-gp		NAa
CLCM-PL	Passive		1.02 μL/min	33.7
	+P-gp		NAa
QECF b			0.2 μL/min
QCSF		Resting period	0.522 μL/min	28.5
		Active period	0.227 μL/min	36.0
VPL b			10.6 mL
VPER 1			7.42 L	5.7
VPER 2			7.09 L	17.3
VDeep Brain b			1440 μL
VECF b			290 μL
VLV b			50 μL
VTFV b			50 μL
VCM b			17 μL
VSAS b			180 μL
Inter-individual variability
CLE			33.2%	17.2
Residual error
PL			42.8%	13.9
ECF			33.0%	13.9
LV			31.9%	18.7
CM			36.2%	13.8
Deep brain			35.6%	13.4
Objective function value			30,298.06

PER1 peripheral compartment 1, PER2 peripheral compartment 2, PL plasma, ECF brain extracellular fluid, LV lateral ventricle, CM cisterna magna, QECF ECF flow, QCSF CSF flow, V volume of distribution of the compartments, TFV third and fourth ventricle, SAS subarachnoid space, +P-gp effect of P-gp-mediated transport on the parameter

^aParameter not available

^bPhysiological values derived from literature (17)