Effects of buprenorphine buccal film and oral oxycodone on pupil diameter in a respiratory study.

OBJECTIVE: Evaluate the pupillary-constricting effects following administration of buprenorphine buccal film (BBF) and immediate-release (IR) oxycodone.

DESIGN: A double-blind, double-dummy, six-treatment, six-period, placebo-controlled, randomized crossover study.

SETTING: Single-center, phase 1 exploratory pharmacodynamics.

PARTICIPANTS: Healthy individuals who self-identify as recreational opioid users, confirmed via a naloxone challenge test on day 1.

INTERVENTIONS: Placebo: BBF 300, 600, and 900 mcg and IR oxycodone 30 and 60 mg.

MAIN OUTCOME MEASURE: Minute ventilation (measured by the ventilatory response to hypercapnia) and pupil diameter (determined via standard pupillometry) were assessed predose and at 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours post-dose.

RESULTS: Change from baseline in minute ventilation was moderately correlated with change from baseline in pupil diameter during treatment with BBF (Pearson's r = 0.38-0.40; p ≤ 0.0011) or oxycodone (Pearson's r = 0.34-0.37; p ≤ 0.005). The initial onset of significant (p < 0.05) pupil constriction relative to placebo occurred at 2, 1.5, and 1 hour after dosing with BBF 300, 600, and 900 mcg, respectively, and at 0.5 hours after dosing with oxycodone 30 or 60 mg.

CONCLUSIONS: Although BBF and IR oxycodone achieved similar levels of pupil constriction, there was a delayed miosis seen with BBF relative to that found with oxycodone.