A pharmacokinetic profile of intranasal hydromorphone in emergency room trauma patients

Intranasal hydromorphone HCl is under development for the management of moderate to severe trauma pain. An element of this investigation was to assess plasma concentrations at near peak times, at the end of a typical dosing interval and across a range of doses being evaluated for relative clinical efficacy and tolerability. Intranasal administration of hydromorphone with a sprayer configured to deliver 2, 4, 6, 8 or 10mg of hydromorphone in 100µL of solution was studied in patients with pain >5 on a 0-10 scale and were evaluated as candidates for opioid treatment. Blood was obtained at baseline and a single dose of intranasal hydromorphone administered. Samples were collected at 30, 60 and 180 minutes following dosing then assayed using LC/MS/MS for plasma hydromorphone concentrations. Patients (n=113) were dosed with 2mg (n=14), 4mg (n=19), 6mg (n=33), 8mg (n=28) or 10mg (n=19) of intranasal hydromorphone. Analysis of plasma hydromorphone demonstrated a dose-related increase at most timepoints. The maximum measured concentration was observed at 30 minutes (mean 2.22ng/mL with 2mg, 4.26ng/mL with 4mg, 5.04ng/mL with 6mg, 6.21ng/mL with 8mg and 7.14ng/mL with 10mg). Concentrations observed following 2mg intranasal doses were similar to those seen for 2mg doses in healthy volunteers. Therapeutic concentrations of hydromorphone in acute pain approximate 4ng/mL. With this intranasal administration at the 30 minute timepoint, 2mg was at or above this concentration in 7% of patients, in 42% of patients with 4mg, in 63% of patients with 6mg, in 81% of patients with 8mg and in 95% of patients with 10mg indicating potential for rapid pain relief. We conclude that for trauma patients presenting to the ER, intranasal administration of this product resulted in rapid absorption of hydromorphone into the plasma. These plasma hydromorphone concentrations are consistent with analgesic concentrations reported in the literature.

Supported by Intranasal Therapeutics, Inc.