Table 5.

Combined parameters of system‐specific and drug‐specific parameters in the PBPK model

		Acetaminophen	Atenolol	Methotrexate	Morphine	Paliperidone	Phenytoin	Quinidine	Raclopride	Remoxipride	Risperidone
Parameter	Unit
QBBB_in	mL/min	0.16	0.12	0.087	0.14	0.33	1.1	9.1	0.18	0.55	1.2
QBBB_out	mL/min	0.31	0.33	4.8	0.38a, 0.62b	0.65	4.4	5.1	0.18	0.69	1.2
QtBBB	mL/min	0.014	0.0075	8.0*10^‐5	0.033	0.24	1.0	7.6	0.086	0.46	1.1
QpBBB	mL/min	0.14	0.11	0.087	0.11	0.090	0.11	0.10	0.099	0.096	0.091
PHF1		1.0	0.80	1.3	0.80	0.80	1.0	0.80	0.80	0.81	0.80
QBCSFB1_in	mL/min	0.019	0.014	0.011	0.015	0.023	0.063	0.52	0.020	0.034	0.063
QBCSFB1_out	mL/min	0.038	0.034	2.2	0.036a, 0.059b	0.042	0.38	0.21	0.013	0.040	0.063
QtBCSFB1	mL/min	6.8*10^‐4	3.6*10^‐4	3.8*10^‐6	0.0016	0.011	0.048	0.36	0.0041	0.022	0.051
QpBCSFB1	mL/min	0.018	0.014	0.011	0.014	0.011	0.014	0.013	0.012	0.012	0.012
PHF2		1.0	0.80	1.3	0.80	0.80	1.0	0.80	0.80	0.81	0.80
QBCSFB2_in	mL/min	0.019	0.014	0.011	0.015	0.023	0.063	0.52	0.017	0.034	0.063
QBCSFB2_out	mL/min	0.040	0.042	4.9	0.044a, 0.073b	0.052	0.38	0.21	0.016	0.047	0.073
QtBCSFB2	mL/min	6.8*10^‐4	3.6*10^‐4	3.8*10^‐6	0.0016	0.011	0.048	0.36	0.0041	0.022	0.051
QpBCSFB2	mL/min	0.018	0.014	0.011	0.014	0.011	0.014	0.013	0.012	0.012	0.012
PHF3		1.0	0.80	1.3	0.80	0.80	1.0	0.80	0.80	0.81	0.80
QBCM_in	mL/min	0.33	0.14	0.0023	0.61	4.4	23	140	1.6	8.4	20
QBCM_out	mL/min	0.33	0.068	0.0046	0.31	2.2	23	70	0.80	4.4	10
PHF4		1.0	0.80	1.3	0.80	0.80	1.0	0.80	0.80	0.81	0.80
PHF5		1.0	0.40	2.5	0.40	0.41	1.0	0.40	0.40	0.42	0.41
QLYSO_in	mL/min	0.16	0.033	0.0022	0.15	1.1	11	33	0.38	2.1	4.8
QLYSO_out	mL/min	0.16	0.00033	0.21	0.0015	0.011	11	0.34	0.0039	0.022	0.049
PHF6		1.0	0.40	2.5	0.40	0.41	1.0	0.40	0.40	0.42	0.41
PHF7		1.0	0.0040	250	0.0041	0.0041	1.0	0.0041	0.0041	0.0044	0.0041
BF		1.1	0.92	NA	1.8a, 3.9b	0.91	8.2	7.2	8.5	5.3	0.49

BBB, blood‐brain barrier; BCM, brain cell membrane; BCSFB, blood‐cerebrospinal fluid barrier; BF, binding factor; LYSO, lysosome; PHF, pH‐dependent factor; Q_BBB, passive diffusion clearance at the BBB; Qt_BBB, transcellular diffusion clearance at the BBB; Qp_BBB, paracellular diffusion clearance at the BBB; Q_BCSFB1, passive diffusion clearance at the BCSFB1; Qt_BCSFB1, transcellular diffusion clearance at the BCSFB1; Qp_BCSFB1, paracellular diffusion clearance at the BCSFB1; Q_BCSFB2, passive diffusion clearance at the BCSFB2; Qt_BCSFB2, transcellular diffusion clearance at the BCSFB2; Qp_BCSFB2, paracellular diffusion clearance at the BCSFB2; Q_BCM, passive diffusion clearance at the brain cell membrane; Q_LYSO, passive diffusion clearance at the lysosomal membrane.

Q_{BBB_in} = Qp_BBB + Qt_BBB*AFin1, Q_{BBB_out} = (Qp_BBB + Qt_BBB*AFout1)*PHF1, Qp_BBB = (aqueous diffusivity coefficient/width_BBB)*SA_BBBp, Qt_BBB = 1/2*transmembrane permeability*SA_BBBt

Q_{BCSFB1_in} = Qp_BCSFB1 + Qt_BCSFB1*AFin2, Q_{BCSFB1_out} = (Qp_BCSFB1+ Qt_BCSFB1*AFout2)*PHF2, Qp_BCSFB1 = (aqueous diffusivity coefficient/width_BCSFB1)*SA_BCSFB1p, Qt_BCSFB1 = 1/2* Transmembrane permeability *SA_BCSFB1t.

Q_{BCSFB2_in} = Qp_BCSFB2 + Qt_BCSFB2*AFin3, Q_{BCSFB2_out} = (Qp_BCSFB2 + Qt_BCSFB2*AFout3)*PHF3, Qp_BCSFB2 = (aqueous diffusivity coefficient/width_BCSFB2)*SA_BCSFB2p, Qt_BCSFB2 = 1/2* transmembrane permeability *SA_BCSFB2t.

Q_{BCM_in} = Transmembrane permeability *SA_BCM*PHF4, Q_{BCM_out} = transmembrane permeability *SA_BCM*PHF5.

Q_{LYSO_in} = transmembrane permeability *SA_LYSO*PHF6, Q_{LYSO_in} = transmembrane permeability *SA_LYSO*PHF7.

PHF1, PHF2, PHF3, PHF4, PHF5, PHF6, and PHF7 were calculated from pKa of each compound and pH of each compartment, respectively.

BF was calculated from Kp of each compound.

^a4 mg/kg.

^b10, 40 mg/kg.