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.