Clinical pharmacokinetics profile of ivermectin 1% cream after dermal applications on the face

Table 1 Demographic characteristics of subjects enrolled in pharmacokinetic studies

	Healthy volunteers PK study (n = 32)	PPR subjects maximal use PK study(n = 17)
Age (yr)
Mean ± SD	30 ± 8	54 ± 12
(Min-max)	(18-45)	(35–74)
Gender (male/female)	16/16	6/11
IGA score: 4 (n %)	NA	17 (100%)
Inflammatory lesion count
Mean ± SD	NA	40.5 ± 14.3
(Min-max)		(27.0-88.0)

NA: Not applicable; PK: Pharmacokinetic; PPR: Papulopustular rosacea.

Table 2 Pharmacokinetic parameters obtained after topical applications of ivermectin 1% cream in healthy volunteer subjects

Group	Time Point	Cmax(ng/mL)	Tmax(h)	AUC0-12 h(ng × h/mL)	AUC0-24 h(ng × h/mL)
1: Single dose	NA	0.49 ± 0.15	9 ± 3	3.8 ± 1.4	8.3 ± 2.5
2: QD 4 wk treatment	Day 0	0.41 ± 0.17	10 ± 5	3.1 ± 1.5	6.9 ± 2.9
	Day 14	0.93 ± 0.35	NA	9.8 ± 3.4	19 ± 7
	Day 28	1.08 ± 0.43	NA	11 ± 5	21 ± 8
3: BID 4 wk treatment	Day 0	0.34 ± 0.16	11 ± 2	2.6 ± 1.5	NA
	Day 14	1.70 ± 0.66	NA	18 ± 6	NA
	Day 28	1.90 ± 0.76	NA	20 ± 9	38 ± 17

NA: Not applicable; AUC_{0-12 h}: Area under the plasma concentration-time curve from pre-application (T0) through to 12 h; AUC_{0-24 h}: Area under the plasma concentration-time curve from pre-application (T0) through to 24 h.

Table 3 Pharmacokinetic parameters of ivermectin obtained after topical application of ivermectin 1% cream once a day in subjects with papulopustular rosacea (maximal use pharmacokinetic study)

ParametersMean ± SD	Day 01	Day 72	Day 14	Day 21	Day 28
Pre-dose/Cmin (ng/mL)	0.37 ± 0.21	1.17 ± 0.88	1.26 ± 0.533	1.36 ± 0.663	1.36 ± 0.63
Cmax (ng/mL)	0.69 ± 0.49	NA	2.10 ± 1.04	NA	1.74 ± 0.77
Tmax (h)	9 ± 6	NA	10 ± 8	NA	11 ± 4
AUC0-24 h (ng × h/mL)	9.3 ± 5.4	NA	36 ± 16	NA	35 ± 14

NA: Not applicable; Pre-dose/C_min: Residual drug concentration (pre-dose level); AUC_{0-24 h}: Area under the plasma concentration-time curve from pre-application (T0) through to 24 h;

¹N: 17;

²N: 13;

³N: 14.

Table 4 Ivermectin plasma concentrations (ng/mL) obtained after repeated topical applications of ivermectin 1% cream QD in subjects with papulopustular rosacea (maximal use pharmacokinetic trial and phase 3 studies #1, #2)

Treatmentduration	Maximal use PK study1	Study #12	Study #23
Week 2	1.3 ± 0.5 (0.6 to 2.3)	NA	NA
Week 4	1.4 ± 0.6 (0.5 to 3.0)	NA	NA
Week 12	NA	0.5 ± 0.7 (< 0.05 to 6.0)	0.4 ± 0.5 (< 0.05 to 2.8)
Week 32	NA	0.4 ± 0.4 (< 0.05 to 3.1)	0.4 ± 0.5 (< 0.05 to 2.9)
Week 52	NA	0.3 ± 0.4 (< 0.05 to 2.2)	0.4 ± 0.6 (< 0.05 to 3.80)

PK: Pharmacokinetic; NA: Not applicable;

¹N: 14 (week 2), n = 15 (week 4);

²N = 105 (week 12), n = 77 (week 32), n = 73 (week 52);

³N= 92 (week 12), n = 84 (week 32), n = 65 (week 52); Note: Data represent Mean ± SD, and minimum to maximum, as available. BLQ data were imputed to the LOQ of 0.05 ng/mL for the maximal use PK study C_min concentration is displayed. For Study #1 and #2 blood samples were taken approximately 12 h after drug application.