TABLE 3

Parameter values used for PBPK modeling

Each parameter is presented as the mean ± S.D., unless otherwise indicated.

Parameters	Units	Model					Initial Value (Range^{^a})
Parameters	Units	1	2	3	4	5	Initial Value (Range^{^a})
V_max,uptake	μmol/h per 78 kg	642	642	1610 ± 159		1750 ± 314	642 (64.2–6420)
K_m,uptake	μM	1.33	1.33	0.534 ± 0.0845		0.667 ± 0.132	1.33 (>0.001)
PS_act	l/h per 78 kg				2360 ± 629		483 (48.3–4830)
PS_dif,inf	l/h per 78 kg	39.1	39.1	5.05 ± 0.729	5.35 ± 2.11	4.22 ± 1.04	39.1 (3.91–391)
PS_dif,eff^{^b}	l/h per 78 kilogram	161	161	20.8	22.0	17.4
V_max,met,OH	μmol/h per 78 kg	97.1	97.1
K_m,met,OH	μM	6.4	6.4
CL_{met,OH,nonsaturable}	l/h per 78 kg	0.936	0.936
V_max,met,DES	μmol/h per 78 kg	44.6	44.6
K_m,met,DES	μM	4.8	4.8
CL_{met,OH,nonsaturable}	l/h per 78 kg	1.62	1.62
V_max,met	μmol/h per 78 kg				868 ± 438	1140 ± 713	135 (13.5–1350)
K_m,met	μM				108 ± 59.4	163 ± 106	5 (>0.001)
CL_int,met	l/h per 78 kg			6.77 ± 0.404			27 (2.7–270)
SF,_transport			10.0 ± 47				1 (0.1–10)
SF,_met			10.0 ± 6.5				1 (0.1–10)
V_c	l/78 kg	6.3	10.5 ± 2.89	7.43 ± 0.953	6.93 ± 2.54	6.94 ± 1.06	6.3 (5.25–10.5)
Final WSS			28.5816	3.01871	6.84816	3.48
AIC			207.166	76.290	125.439	86.8143

CL_{,met_OH},_nonsaturable, nonsaturable CL_met for the production of hydroxyl bosentan; SF,_met, scaling factors for V_max for the production of desmethyl bosentan, V_max for the production of hydroxyl bosentan, and CL_met; SF,_transport, scaling factors for V_max,uptake and PS_dif; V_c, distribution volume of the central compartment; V_max,met,DES, V_max,met for the production of desmethyl bosentan; V_max,met,OH, V_max,met for the production of hydroxyl bosentan.
↵^a Range is the constraint on the estimates for each parameter in model fitting to data.
↵^b Calculated by PS_dif,inf and γ.