Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects

Table 1

Pharmacokinetic parameters for morphine after administration of crushed intranasal Morphine ARER, crushed intranasal ER morphine, or intact oral Morphine ARER (PK population, ).

Parameter	Mean (SD)
	Intact oral Morphine ARER	Crushed intranasal Morphine ARER	Crushed intranasal ER morphine
Cmax (ng/mL)	18.6 (5.7)	26.2 (11.2)	49.5 (17.3)
Tmax (hr)	1.6 (0.5–3.1)	1.6 (1.0–3.1)	1.1 (0.2–1.6)
AUC0–t (ng · hr/mL)	139.4 (40.1)	178.5 (77.7)	171.6 (55.2)
AUC0–∞ (ng · hr/mL)	158.0 (21.9)	219.8 (97.4)^†	188.0 (51.5)^‡
ke (hr^−1)	0.0688 (0.0399)^§	0.0997 (0.0649)^‖	0.0684 (0.0583)
t1/2 (hr)	18.4 (20.0)^§	10.8 (8.3)^‖	21.0 (20.9)
AUC0–0.5h (ng · hr/mL)	2.1 (1.3)	2.8 (1.2)	10.9 (5.2)
AUC0–1 (ng · hr/mL)	7.5 (3.2)	11.2 (4.8)	30.8 (12.1)
AUC0–2h (ng · hr/mL)	22.6 (7.5)	34.2 (13.7)	67.0 (22.9)
AUC0–8h (ng · hr/mL)	89.3 (25.4)	120.9 (48.2)	136.5 (43.4)
AUC0–12h (ng · hr/mL)	105.6 (29.5)	143.2 (57.8)	148.1 (47.4)
AUC0–24h (ng · hr/mL)	139.4 (40.1)	181.1 (75.9)	171.6 (55.2)

for crushed intranasal ER morphine and for both Morphine ARER treatments, except as noted: , ^†, ^‡, ^§, ^‖; AUC_{0–0.5, 0–1, 0–2, 0–8, 0–12, 0–24} = area under the plasma concentration-time curve from 0 h to 0.5 h, 1 h, 2 h, 8 h, 12 h, and 24 h; AUC_0–t = area under the plasma concentration-time curve from 0 h to the last measurable concentration above the lower limit of quantification; AUC_0–∞ = area under the plasma concentration-time curve from 0 h to infinity; C_max = maximum observed plasma concentration; ER = extended release; h = hour; k_e = elimination rate constant; PK = pharmacokinetic; T_max = time associated with C_max; t_1/2 = half-life; values for T_max are medians and ranges.