Comparison of the systemic bioavailability of mometasone furoate after oral inhalation from a mometasone furoate/formoterol fumarate metered-dose inhaler versus a mometasone furoate dry-powder inhaler in patients with chronic obstructive pulmonary disease

Figures & data

Table 1 MF and F pharmacokinetic parameters on day 5 following twice-daily administration of MF/F MDI with or without a spacer or MF DPI in patients with chronic obstructive pulmonary disease

Parameter	n	MF/F MDI Treatment A		MF/F MDI + spacer Treatment B		MF DPI Treatment C
		MF	Formoterol	MF	Formoterol	MF
Tmax (median), h Median (range)	14	3.00 (0.50–8.00)	1.02 (0.18–2.02)	2.00 (0.50–8.00)	0.52 (0.18–4.02)	1.00 (0.50–12.0)
Cmax, mean (CV [%])	14	49.2 (55) (pg/mL)	23.78 (24) (pmol/L)	41.1 (45) (pg/mL)	20.77 (47) (pmol/L)	90.2 (48) (pg/mL)
AUC0–12 hr, mean (CV [%])	14	484 (56) (pg · h/mL)	152.9 (26) (pmol · h/L)	353 (44) (pg · h/mL)	101.1 (39) (pmol · h/L)	646 (47) (pg · h/mL)

Notes: MF/F MDI (treatment A) = MF 400 μg/F 10 μg inhaled orally twice a day via MDI without a spacer device; MF/F MDI + spacer (treatment B) = MF 400 μg/F 10 μg inhaled orally twice a day via MDI with a spacer device; MF DPI (treatment C) = MF 400 μg inhaled orally twice a day via DPI.

Abbreviations: AUC_{0–12 hr}, area under the concentration–time curve from 0 hours to 12 hours on day 5; C_max, mean maximum concentration; CV, coefficient of variation; DPI, dry-powder inhaler; F, formoterol fumarate; MDI, metered-dose inhaler; MF, mometasone furoate; T_max, time to C_max.

Figure 1 Mean (SD) MF plasma concentration-time profiles at day 5 in patients with chronic obstructive pulmonary disorder.

Notes: Subjects received the following treatments by oral inhalation twice-daily for 5 consecutive days: MF 400 μg/F 10 μg via MDI without a spacer device (MF/F MDI; treatment A); MF 400 μg/F 10 μg via MDI with a spacer device (MF/F MDI with spacer; treatment B); and MF 400 μg via DPI (MF DPI; treatment C). Inset shows graph with log scale for y-axis (MF plasma concentration).
Abbreviations: DPI, dry-powder inhaler; F, formoterol fumarate; MDI, metered-dose inhaler; MF, mometasone furoate; SD, standard deviation.

Table 2 Day 5 exposures to MF following twice-daily administration of MF/F MDI with or without a spacer or MF DPI in patients with chronic obstructive pulmonary disorder

Parameter	n	Least squares geometric meana			Intrapatient CV	Treatment comparison	GMR (%)	90% CI
		MF/F MDI Treatment A	MF/F MDI + spacer Treatment B	MF DPI Treatment C
AUC0–12 hr (pg · hour/mL)	14	431	322	561	44%	A versus C	77	58–102
						B versus A	75	56–100
Cmax (pg/mL)	14	44	37	77	47%	A versus C	56	41–77
						B versus A	86	63–117
Ctrough (pg/mL)	14	28	17	26		A versus C	106	80–142
						B versus A	62	51–75

Notes:

a Model-based (least squares) mean: ANOVA model extracting the effects due to treatment, sequence, period, and patient. MF/F MDI (treatment A) = MF 400 μg/F 10 μg inhaled orally twice a day via MDI without a spacer device; MF/F MDI + spacer (treatment B) = MF 400 μg/F 10 μg inhaled orally twice a day via MDI with a spacer device; MF DPI (treatment C) = MF 400 μg inhaled orally twice a day via DPI.

Abbreviations: ANOVA, analysis of variance; AUC_{0–12 hr}, area under the concentration–time curve from 0 hours to 12 hours on day 5; CI, confidence interval; C_max, mean maximum concentration; C_trough, trough plasma concentration; CV, coefficient of variation; DPI, dry-powder inhaler; F, formoterol fumarate; GMR, geometric mean ratio; MDI, metered-dose inhaler; MF, mometasone furoate; T_max, time to C_max.

Table 3 Day 5 exposures to MF and formoterol following twice-daily administration of MF/F MDI with or without a spacer in patients with chronic obstructive pulmonary disorder

Parameter	n	Least squares geometric meana,b		Intrapatient CV	Treatment comparison	GMR (%)	90% CI (%)
		MF/F MDI Treatment A	MF/F MDI + spacer Treatment B
Mometasone furoate
AUC0–12 hr (pg · h/mL)	14	429	309	23%	B versus A	72	61–84
Cmax (pg/mL)	14	44	36	24%	B versus A	82	69–97
Formoterol
AUC0–12 hr (pmol · h/L)	14	150	93	–	B versus A	62	52–74
Cmax (pmol/L)	14	23.3	18.5	–	B versus A	80	63–101

Notes:

a Model-based (least squares) mean: ANOVA model extracting the effects due to treatment, sequence, period, and patient;

b based on analyses excluding treatment C (MF 400 μg inhaled orally twice a day via dry powder inhaler). MF/F MDI (treatment A) = MF 400 μg/F 10 μg inhaled orally twice a day via metered-dose inhaler without a spacer device; MF/F MDI + spacer (treatment B) = MF 400 μg/F 10 μg inhaled orally twice a day via metered-dose inhaler with a spacer device. Because data for treatment C had higher variability than data for treatments A and B, analyses excluding treatment C were performed as sensitivity analyses.

Abbreviations: ANOVA, analysis of variance; AUC_{0–12 hr}, area under the concentration-time curve from 0 hours to 12 hours postdose; CI, confidence interval; C_max, maximum plasma concentration; CV, coefficient of variation; F, formoterol fumarate; GMR, geometric mean ratio; MDI, metered-dose inhaler; MF, mometasone furoate.

Figure 2 Mean (SD) formoterol plasma concentration-time profiles at day 5 after twice-daily oral inhalation of MF/F MDI (MF 400 μg/F 10 μg) with (treatment B) and without (treatment A) a spacer device in patients with chronic obstructive pulmonary disorder.

Note: Inset shows graph with log scale for y-axis (formoterol plasma concentration).
Abbreviations: F, formoterol fumarate; MDI, metered-dose inhaler; MF, mometasone furoate; SD, standard deviation.