. 2023 Nov 22;14:1234262. doi: 10.3389/fphar.2023.1234262

TABLE 2.

Dosing regimens and demographic characteristics in the simulations of PBPK model development and validation.

Drug	Dosage schedules	Purpose	Virtual population	Number of virtual subjects^a	Age range set (year)	Proportion of female (%)	Source of data or comments
CRI	50 mg intravenous dosing, SD	Validate plasma PK data when dosed alone	Healthy	14	18–55	0	Xu et al. (2015a)
	250 mg OD, SD		Healthy	14	18–55	0	Xu et al. (2015a)
	250 mg OD, RD for consecutive 14 days		Patients	10	40–75	78	Kurata et al. (2015)
	Multiple doses for 50–300 mg, RD for consecutive 28 days		Patients	10	25–73	42	Age range was set based on mean age of 49 (Clark et al., 2019)
	250 mg OD, SD		Healthy	10	26–53	0	Huiping et al. (2022)
	100 mg OD, RD for consecutive 14 days	Validate intracranial concentration	Patients	10	30–70	50	Demographic data were set in this study
	➀CRI: 150 mg, SD, on day 4	Validate plasma PK variation when dosed with CYP3A4 perpetrators	Healthy	16	26–53	0	Xu et al. (2015a)
	➁Ketoconazole: 200 mg BID, RD from days 1 to 16		Healthy	15	29–44	0	Xu et al. (2015b)
	➀CRI: 250 mg, SD, on day 9		Healthy	15	38–47	7
	➁Rifampin: 600 mg OD, RD from days 1 to 14		Healthy	15	38–47	7
ALE	600 mg OD, SD	Validate plasma PK when dosed alone	Healthy	16	26–53	0	Morcos et al. (2017c)
	160, 240, and 300 mg BID, RD for consecutive 21 days		Patients	10	28–67	54	Seto et al. (2013)
	460, 600, and 900 mg BID, RD for consecutive 21 days		Patients	10	40–83	20	Gadgeel et al. (2014)
	600 mg OD, RD for days 1–14	Validate intracranial concentration	Patients	10	36–76	50	Age range was set based on mean age of 56 (Gainor et al., 2016)
	➀ALE: 300 mg, SD, on day 6	Validate plasma PK variation when dosed with CYP3A4 perpetrators	Healthy	10	30–70	50	Demographic data were set in this study
	➁Posaconazole: 400 mg BID, RD from days 1 to 14
	➀ALE: 150 mg, SD, on day 6
	➁Rifampin: 600 mg OD, RD from days 1 to 14
LOR	50 mg intravenous dosing, SD	Validate plasma PK when dosed alone	Healthy	11	18–55	0	Hibma et al. (2022)
	100 mg OD, SD		Healthy	11	18–55	0	Hibma et al. (2022)
	100 mg OD, RD for consecutive 15 days		Patients	19	39–65	32	Chen et al. (2021)
	100 mg OD, SD		Patients	10	53–61	38	Lin et al. (2022)
	100 mg OD, RD for consecutive 21 days	Validate intracranial concentration	Patients	10	30–70	50	Sun et al. (2022)
	➀LOR: 150 mg, SD, on day 5	Validate plasma PK variation when dosed with CYP3A4 perpetrators	Healthy	16	20–54	0	Patel et al. (2020)
	➁Itraconazole: 200 mg BID, RD from days 1 to 11		Healthy	16	20–54	0	Patel et al. (2020)
	➀LOR:150 mg, SD, on day 13		Healthy	12	21–55	8.3	Chen et al. (2020)
	➁Rifampin: 600 mg OD, RD from days 6 to 17		Healthy	12	21–55	8.3	Chen et al. (2020)

BID, twice daily; SD, single dose; RD, repeated doses.