Table 5.

Gastroplus PBPK model input parameters.

	Adult Model	References
Population	Healthy Volunteers
Drug Parameters
Physicochemical properties
Molecular weight (g/mol)	804.02	[36]
Log Po:w	3.26	[36]
Compound type	neutral	[36]
Absorption
ACAT model
Peff (10−4 cm/s)	4.77	[26]
Formulation	IR Capsule
Solubility @ pH 4.5 ABS buffer—Amorphous formulation (mg/mL) (Reference solubility)	0.06257	In-house data
SGF solubility—Amorphous formulation (mg/mL)	0.07412	In-house data
FaSSIF Solubility—Amorphous formulation (mg/mL)	0.19655	In-house data
FeSSIF Solubility—Amorphous formulation (mg/mL)	0.60547	In-house data
Solubilization ratio—Amorphous formulation	30300	Gastroplus fitted
Solubility @ pH 4.5 ABS buffer—Crystalline (mg/mL)	0.00165	In-house data
SGF solubility—Crystalline (mg/mL)	0.01003	In-house data
FaSSIF Solubility—Crystalline (mg/mL)	0.00678	In-house data
FeSSIF Solubility—Crystalline (mg/mL)	0.01746	In-house data
Solubilization ratio—Crystalline	11400	Gastroplus fitted
Mean particle radius (µm)	25	Default value in Gastroplus
Mean precipitation time (sec)	900	Default value in Gastroplus
Particle density (g/mL)	1.2	Default value in Gastroplus
Distribution
Distribution model	none used
PSA input
Dose (mg)	10.5, 5, 2.5, 1.25 or 0.625
PSA analysis setup	Input value
Small intestine fluid volume (minimum)	0.28% filled (4.0 mL)
Small intestine fluid volume (baseline)	3.15% filled (45.2 mL)
Small intestine fluid volume (maximum)	15.75% filled (225.5 mL)
Precipitation time (minimum)	0.1 s
Precipitation time (baseline)	90 s
Precipitation time (maximum)	900 s

ACAT model = advanced compartmental absorption and transit model; P_eff = effective permeability.