PI-091 - THE DORSAL FOREARM AS A NOVEL TARGET FOR INTRAMUSCULAR INJECTIONS: CLINICAL PHARMACOKINETIC RESULTS.

T. Krol¹, B. Beutel², C. Fierro³, S. Weir⁴; ¹STAT Therapeutics, Inc, KS, United States, ²Kansas City University, Kansas City, MO, United States, ³STAT Therapeutics, Inc, Lenexa, KS, United States, ⁴STAT Therapeutics, Inc, Kansas City, KS, United States.

Background: The dorsal forearm represents a potential viable location for a convenient wearable device for the administration of intramuscular (IM) injections, but this site has not previously been formally targeted for this purpose. The objectives of this study were to administer naloxone via IM injection into the dorsal forearm, characterize the pharmacokinetic (PK) profile of this injection site and mode, and compare to that of a standard IM injection.

Methods: The study was an outpatient, open-label, single period, single treatment, single dose proof of concept (PoC) trial in 12 healthy subjects. After screening, participants provided a time zero (pre-dose) blood sample and then were administered 2 mg naloxone HCl as an IM injection in the extensor digitorum communis (EDC) muscle of the dorsal forearm. Serial blood (plasma) samples were obtained from the contralateral arm at the following time points: 5 minutes prior to dosing and 5, 10, 15, 20, 30, 40, and 50 minutes and 1, 1.25, 1.5, 2, 3, 4, and 6 hours post-dose. Plasma naloxone concentrations were determined using a validated LC MS/MS assay. PK parameters were generated from the resultant plasma naloxone concentration-time data for each IM injection site using WinNonLin 8.4.

Results: The means and ranges of the PK profile of naloxone administered IM in the forearm were: Cmax 5.3 ng/mL (2.21 - 11.07); Tmax 0.29 h (0.08 - 0.67); AUC[0-∞] 7.96 ng*h/mL (5.85 to 10.68); T1/2 1.36 h (0.95 - 1.74). The relative bioavailability of naloxone administered into the dorsal forearm was 87% compared to IM naloxone administered in the thigh. The subjects noted minimal discomfort with the forearm injection, and there were no adverse neurovascular events.

Conclusion: This is the first time a drug has been administered in the EDC of the dorsal forearm as an IM target muscle. IM administration of naloxone in the dorsal forearm has a PK profile nearly equivalent to IM injection in the thigh. This new injection site was associated with minimal discomfort and no complications. These results demonstrate that a novel platform medical device, that can inject a product like naloxone into the dorsal forearm, may be a more versatile and convenient alternative to other IM routes of administration.