Table 4.

Pharmacokinetic parameters of vilaprisan (VPR) parent after single oral or intravenous administration of VPR without or with concomitant administration of itraconazole (ITZ) 200 mg/day

Study		MB study VPRa Oral		DDI study VPRb Oral		DDI study VPR + ITZc Oral		MT sub-study VPRd Intravenous
Treatment
Route of administration
Parameter	Unit	N = 6		N = 14		N = 14		N = 7
		gMean (CV%)	[Range]	gMean (CV%)	[Range]	gMean (CV%)	[Range]	gMean (CV%)	[Range]
AUC	µg·h/L	324 (38.0)	[217–504]	325 (42.3)	[191–607]	N/C		2170 (35.9)	[1410–3500]
AUC0–24	µg·h/L	N/C		146 (29.5)	[95.8–217]	302 (18.9)	[238–388]	980 (26.2)	[731–1330]
AUC0–3d	µg·h/L	N/C		247 (33.4)	[153–393]	740 (18.1)	[586–970]	N/C
AUC0–11d	µg·h/L	N/C		321 (41.3)	[190–580]	2000 (18.4)	[1520–2740]	N/C
${\text{AUC}}_{0-t_{\text{last}}}$	µg·h/L	317 (38.3)	[212–495]	317 (42.6)	[184–591]	2000 (18.4)	[1520–2730]	2100 (35.4)	[1340–3300]
C max	µg/L	24.9 (38.5)	[15.3–41.2]	16.6 (32.3)	[9.14–24.5]	29.5 (19.5)	[21.9–38.7]	277 (29.7)	[168–389]
t 1/2	h	31.6 (24.7)	[22.6–44.1]	38.9 (20.7)	[29.0–60.7]	N/C		42.4 (20.7)	[28.6–56.7]
t max	h	1.00e	[1.00–2.00]	2.50e	[1.42–4.00]	2.25e	[1.50–3.00]	0.483e	[0.333–0.483]
t last	h	144e	[120–240]	204e	[144–312]	263e	[263–263]	215e	[167–215]
CL/F or CL	L/h	15.1 (38.0)	[9.7–22.4]	12.3 (42.3)	[6.59–21.0]	N/C		7.22 (35.9)	[4.47–11.1]
Vz/F or Vz	L	691 (27.4)	[492–978]	N/C		N/C		442 (33.8)	[302–713]
V ss	L	–		–		–		359 (23.4)	[277–479]
MRTIV	h	–		–		–		49.7 (19.1)	[38.0–68.3]
F	%	–		–		–		61.1	[53.1–69.5]

AUC_0–t area under the concentration–time curve from time zero to time t, CL total body clearance of drug from plasma calculated after intravenous administration, CL/F total body clearance of drug from plasma calculated after oral administration (apparent oral clearance), C_max maximum plasma concentration, CV% coefficient of variation [%], DDI drug–drug interaction, F absolute oral bioavailability, gMean geometric mean, MB mass balance, MRT_IV mean residence time after intravenous administration, MT microtracer, N/C not calculated, t_1/2 terminal half-life, t_last time of last concentration above lower limit of quantitation, t_max time to reach C_max, V_ss volume of distribution at steady state, V_z volume of distribution during terminal phase

Figures were rounded to three significant digits

F was calculated as follows: $F=\frac{{\text{AUC}}_{\text{PO}}}{{\text{AUC}}_{\text{IV}}}\times \frac{{\text{Dose}}_{\text{IV}}}{{\text{Dose}}_{\text{PO}}}$

^a[¹⁴C]VPR 5 mg

^bVPR 4 mg

^cVPR 4 mg on the fourth day of concomitant treatment with ITZ 200 mg/day

^dIntravenous microdose of [¹⁴C]VPR 15.7 µg (37 KBq) 1.5–2 h after oral administration of VPR 4 mg (30-min infusion)

^eMedian (range)