Comparison of a New Intranasal Naloxone Formulation to Intramuscular Naloxone: Results from Hypothesis-generating Small Clinical Studies.

Easy-to-use naloxone formulations are needed to help address the opioid overdose epidemic. The pharmacokinetics of i.v., i.m., and a new i.n. naloxone formulation (2 mg) were compared in six healthy volunteers. Relative to i.m. naloxone, geometric mean (90% confidence interval [CI]) absolute bioavailability of i.n. naloxone was modestly lower (55%; 90% CI, 43-70% vs. 41%; 90% CI, 27-62%), whereas average (+/- SE) mean absorption time was substantially shorter (74 +/- 8.8 vs. 6.7 +/- 4.9 min). The opioid-attenuating effects of i.n. naloxone were compared with i.m. naloxone (2 mg) after administration of oral alfentanil (4 mg) to a separate group of six healthy volunteers pretreated with 240 mL of water or grapefruit juice. The i. m. and i.n. naloxone attenuated miosis by similar extents after water (40 +/- 15 vs. 41 +/- 21 h*%) and grapefruit juice (49 +/- 18 vs. 50 +/- 22 h*%) pretreatment. Results merit further testing of this new naloxone formulation.