TABLE 2.

Prediction of DDI between DABE and CYP3A/P-gp inhibitors using the final PBPK models of DABE and its metabolites.

Set	DABE		Perpetrators	Cmax ratio			AUC0-inf ratio			References
	Dose	Formulation		Observed	Simulated	Criteria a	Observed	Simulated	Criteria a
Training sets
1	375 µg	Solution with precipitation	CTC 500 mg PO BID 5 days	4.57 (2.85–7.34)	4.46 (4.17–4.78)	2.57–8.14	4.02 (2.99–5.41)	4.64 (4.33–4.97)	2.30–7.04	Prueksaritanont et al. (2017)
2	300 mg	Solid IR	CTC 500 mg PO BID 5 days	1.60#	1.61#	1.16–2.20	1.49#	1.97#	1.12–1.98	Delavenne et al. (2013)
Qualification sets
6	750 µg	Solution with precipitation	RF 600 mg PO SD	1.86 (1.43–2.43)	2.16 (2.08–2.23)	1.27–2.72	2.22 (1.74–2.83)	1.94 (1.88–1.99)	1.49–3.68	Rattanacheeworn et al. (2021)
7	375 µg	Solution with precipitation	ITZ 200 mg (solution) PO QD 5 days	6.42 (4.57–9.01)	4.82 (4.48–5.19)	3.48–11.84	6.92 (4.96–9.66)	5.12 (4.74–5.52)	3.73–12.84	Prueksaritanont et al. (2017)
8	375 µg	Solution wth precipitation	RF 600 mg PO SD	1.78 (1.47–2.16)	2.16 (2.09–2.24)	1.24–2.56	2.32 (1.86–2.90)	1.94 (1.89–1.99)	1.51–3.76	Prueksaritanont et al. (2017)
9	300 mg	Solid IR	CTC 500 mg PO BID 5 days	1.71	1.61	1.21–2.42	1.97	1.97	1.32–2.94	Gouin-Thibault et al. (2017)
10	150 mg	Solid IR	VP IR 120 mg PO SD	2.15	1.55	1.40–3.30	1.98	1.88	1.32–2.96	Hartter et al. (2013)
11	150 mg	Solid IR	VP IR 120 mg PO SD 1 h before DABE	2.70	1.74	1.66–4.40	2.37	2.07	1.50–3.74	Hartter et al. (2013)

Data were reported as geometric means (90% confidence interval or % coefficient of variation), except. ^# median.

^a Acceptance range was defined based on Guest’s DDI, prediction criteria (Guest et al., 2011).