Table 1.

Summary details including the dosing details and observed AUC ratio of the 35 in vivo DDI studies between three azoles and three benzodiazepines used for assessment of the static and dynamic models

Inhibitor	Inhibitor dose	Dosing start day and time	Dosing interval (h)	Number of doses	Victim drug	Victim drug dose	Victim drug dosing time	Observed AUC ratio	Reference
Fluconazole	400 mg	Day 1, 13.00 h	SD	1	Midazolam	7.5 mg	Day 1, 14.00 h	3.73	[35]
Fluconazole	100 mg	Day 1	SD	1	Midazolam	3 mg	Day 1, +2 h	2.16	[37]
Fluconazole	200 mg	Day 1	SD	1	Midazolam	3 mg	Day 1, +2 h	3.32	[37]
Fluconazole	400 mg	Day 1	SD	1	Midazolam	3 mg	Day 1, +2 h	4.93	[37]
Fluconazole	400 mg	Day 1, 13.00 h	SD	1	Midazolam	7.5 mg	Day 1, 15.00 h	3.51	[39]
Fluconazole	400 mg/200 mg	400 mg Day 1, 13.00 h, 200 mg Day 2–6, 13.00 h	24	6	Midazolam	7.5 mg	Day 6, 15.00 h	3.60	[39]
Fluconazole	100 mg	Day 1–4, 14.00 h	24	4	Triazolam	0.25 mg	Day 4, 15.00 h	2.46	[42]
Fluconazole	50 mg	Day 1–4, 13.00 h	24	4	Triazolam	0.25 mg	Day 4, 14.00 h	1.63	[43]
Fluconazole	100 mg	Day 1–4, 13.00 h	24	4	Triazolam	0.25 mg	Day 4, 14.00 h	2.05	[43]
Fluconazole	400 mg/200 mg	400 mg Day 1, 13.00 h, 200 mg Day 2–4, 13.00 h	24	4	Triazolam	0.25 mg	Day 4, 14.00 h	4.42	[43]
Ketoconazole	200 mg	Day 1–3, 08.00 h	12	5	Alprazolam	1 mg	Day 3, 09.00 h	3.98	[44]
Ketoconazole	200 mg	Day 1–3	12	5	Alprazolam	1 mg	Day 3	1.76	[45]
Ketoconazole	200 mg	Day 1–3	12	5	Midazolam	0.075 mg	Day 3	6.47	[46]
Ketoconazole	200 mg	Day 1–12	24	12	Midazolam	10 mg	Day 12, +1 h	6.56	[47]
Ketoconazole	400 mg	Day 1–4, 14.00 h	24	4	Midazolam	7.5 mg	Day 4, 15.00 h	15.9	[48]
Ketoconazole	200 mg	Day 1–2	12	3	Midazolam	6 mg	Day 1, +12 h*	16.0	[49]
Ketoconazole	200 mg	Day 1–2	12	3	Midazolam	5 mg	Day 1, +13 h*	8.10	[50]
Ketoconazole	400 mg	Day 1–10	24	10	Midazolam	5.5 mg	Day 9	9.51	[51]
Ketoconazole	200 mg	Day 1, 07.00 h	SD	1	Midazolam	2 mg	Day 1, 09.00 h	4.95	[36]
Ketoconazole	200 mg	Day 1, 09.00 h	SD	1	Midazolam	2 mg	Day 1, 09.00 h	6.45	[36]
Ketoconazole	200 mg	Day 1–3, 08.00 h	12	5	Triazolam	0.25 mg	Day 3, 09.00 h	13.7	[44]
Ketoconazole	400 mg	Day 1–4, 14.00 h	24	4	Triazolam	0.25 mg	Day 4, 15.00 h	9.17	[40]
Ketoconazole	200 mg	Day 1–2	16	2	Triazolam	0.125 mg	Day 2, +1 h	9.16	[52]
Itraconazole	200 mg	Day 1–6, 08.00 h	24	6	Alprazolam	0.8 mg	Day 4, 09.00 h	2.66	[53]
Itraconazole	100 mg	Day 1–4, 13.00 h	24	4	Midazolam	7.5 mg	Day 4, 15.00 h	5.75	[54]
Itraconazole	200 mg	Day 1–4, 11.00 h	24	4	Midazolam	7.5 mg	Day 4, 13.00 h	6.16	[55]
Itraconazole	200 mg	Day 1–4, 11.00 h	24	4	Midazolam	7.5 mg	Day 8, 13.00 h	2.51	[55]
Itraconazole	200 mg	Day 1–4, 14.00 h	24	4	Midazolam	7.5 mg	Day 4, 15.00 h	10.8	[48]
Itraconazole	200 mg	Day 1, 13.00 h	SD	1	Midazolam	7.5 mg	Day 1, 15.00 h	3.42	[39]
Itraconazole	200 mg	Day 1–6, 13.00 h	24	6	Midazolam	7.5 mg	Day 6, 15.00 h	6.64	[39]
Itraconazole	200 mg	Day 1, 15.00 h	SD	1	Triazolam	0.25 mg	Day 2, 15.00 h	3.57	[38]
Itraconazole	200 mg	Day 2, 03.00 h	SD	1	Triazolam	0.25 mg	Day 2, 15.00 h	4.33	[38]
Itraconazole	200 mg	Day 2, 12.00 h	SD	1	Triazolam	0.25 mg	Day 2, 15.00 h	4.48	[38]
Itraconazole	200 mg	Day 2, 15.00 h	SD	1	Triazolam	0.25 mg	Day 2, 15.00 h	3.11	[38]
Itraconazole	200 mg	Day 1–4, 14.00 h	24	4	Triazolam	0.25 mg	Day 4, 15.00 h	10.5	[40]

If exact timings were not reported, the substrate dosing time is given as plus a number of hours after the final inhibitor dose.

^*The exception was where the substrate was given with or 1 h after the second inhibitor dose.

SD, Single dose.