Absorption of naloxone in patients prescribed buprenorphine-naloxone

When administered as prescribed, the naloxone component of buprenorphine-naloxone combination medications is putatively considered inert due to reduced naloxone bioavailability via transmucosal. However, there is a growing body of evidence to the contrary. The aim of our study is to determine the extent of naloxone absorption in a large cohort of patients receiving sublingual buprenorphine-naloxone.

Using the Mayo Clinic Unified Data Platform, 425 patients prescribed sublingual buprenorphine/naloxone who received a controlled substance monitoring panel (CSMP) between January 1, 2022, and January 1, 2023 were identified and included. The CSMP is an immunoassay panel that confirms positive results quantitatively with gas chromatography mass spectrometry or liquid chromatography tandem mass spectrometry. This panel provides urinary detection for buprenorphine (cutoff: 5 ng/mL), naloxone (25 ng/mL), as well as their respective metabolites norbuprenorphine (5 ng/mL), norbuprenorphine-glucuronide (20 ng/mL), and naloxone-glucuronide (100 ng/mL).

Of our 425 patients, 76% had norbuprenorphine (n = 323), and 77% had norbuprenorphine-glucuronide (n = 327) in their toxicology tests, respectively. Naloxone-glucuronide was detected in 91% (n = 294) of the specimens with norbuprenorphine and 88.7% (n = 290) of the specimens with norbuprenorphine-glucuronide.

To our knowledge, this is the largest study to date demonstrating the presence of naloxone metabolites in patients taking combined buprenorphine-naloxone medications. The results of this study refute the notion that naloxone absorption is negligible when administered in sublingual preparations. Further research on how this absorption impacts medication usage, dosing, adherence, and side effects is necessary.