Opioid Delivery to Olfactory Region Ups Therapeutic Effects

More of drug delivered to central nervous system, no increase in plasma drug exposure in rats

FRIDAY, Sept. 9 (HealthDay News) -- Administration of opioids directly to the nasal olfactory region results in a larger fraction of drug being delivered to the central nervous system (CNS) and a significantly higher therapeutic effect without an increase in plasma drug exposure compared to drug delivery to the nasal respiratory region in rats, according to an experimental study published in the September issue of Anesthesia & Analgesia.

John D. Hoekman, Ph.D., and Rodney J.Y. Ho, Ph.D., from the University of Washington in Seattle, investigated whether opioids, such as morphine and fentanyl, show higher efficacy when administered though the olfactory region in Sprague-Dawley rats using a pressurized olfactory delivery (POD) device. Tail-flick latency test and analysis of plasma and CNS tissue drug exposure were used to compare the efficacy and distribution of opioids to the nasal olfactory region with the POD device, or the nasal respiratory region with nose drops or systemically via intraperitoneal injection.

The investigators found that, compared with drops, POD administration showed a significantly increased overall therapeutic effect without significantly increasing the plasma drug exposure. Between 38 to 55 percent of the morphine dose was transported directly from the nose to the CNS using the POD device. Compared with nasal respiratory administration, POD of fentanyl showed faster (10 versus 5 minutes) and more intense analgesic effects. Morphine and fentanyl administered to the olfactory region exhibited clockwise (plasma) versus effect hysteresis after nasal POD administration, which was consistent with a direct nose-to-CNS drug transport mechanism as opposed to intraperitoneal injection or nose-drop administration.

"Deposition of opioids to the olfactory region within the nasal cavity could have a significant impact on drug distribution and pharmacodynamic effect," the authors write.

Both authors disclosed financial ties to Impel NeuroPharma Inc., and hold a patent for the POD nasal spray device.

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