Sublingual Buprenorphine/Naloxone Film in Unanesthetized Rats: Feasibility, Tolerability, and Plasma Exposure
ABSTRACT Background Buprenorphine/naloxone sublingual film is first-line treatment for opioid use disorder, yet preclinical rodent studies use routes that do not match clinical dosing. We tested sublingual film administration in unanesthetized rats. Methods Male Sprague-Dawley rats received film delivering 3.2 mg/kg buprenorphine, scaled from the 16 mg/day clinical dose by body surface area and…
Buprenorphine/naloxone sublingual film has been found feasible and well-tolerated in unanesthetized rats, according to preclinical rodent studies. The film delivers a dose equivalent to the 16 mg/day clinical dose, adjusted for differences in sublingual bioavailability between humans and rats. After administration of a single dose, plasma buprenorphine levels peaked at 4.0 ng/mL within two hours and remained at 0.9 ng/mL after 24 hours, falling within the therapeutic range reported in patients.
Plasma buprenorphine exposure was sustained over a 24-hour period, spanning concentrations previously associated with therapeutic effects in patients. Repeated dosing resulted in a decrease in absolute and relative liver weight, as well as relative weight of the liver, without any changes to serum enzymes or liver histopathology.
These findings suggest that sublingual film dosing is a viable alternative for route-matched preclinical studies examining buprenorphine pharmacology and opioid-related behaviors.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
