Faculty, Staff and Student Publications

Language

English

Publication Date

9-1-2025

Journal

Journal of Addiction Medicine

DOI

10.1097/ADM.0000000000001401

PMID

39621545

PMCID

PMC12127498

PubMedCentral® Posted Date

12-2-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Objectives: The US Food and Drug Administration (FDA) issued a warning about buprenorphine-induced dental caries of unknown mechanism in 2022. To investigate the potential mechanism, the association between local buprenorphine exposure and dental biofilm formation will be explored in this study.

Methods: Female F344 rats were dosed with sublingual buprenorphine film or intravenous injection to explore the oral cavity exposure of the buprenorphine. The buprenorphine distribution in salivary glands after the sublingual and intravenous administration was also evaluated. To investigate the effects of buprenorphine exposure on dental caries formation, buprenorphine's impact on the biofilm formation of S. mutans in vitro was measured.

Results: The absolute sublingual bioavailability of buprenorphine in rats was 17.8% with a high ratio of oral fluid exposure to blood concentration in the pharmacokinetic study. Salivary gland concentrations of buprenorphine and its active metabolite norbuprenorphine were significantly higher than their blood concentrations after both sublingual (s.l.) and intravenous (i.v.) administration. Correlation analysis showed that the oral fluid concentration of buprenorphine and norbuprenorphine was highly correlated to salivary gland concentration rather than blood concentration. These data indicate that the salivary gland serves as an accumulation organ for buprenorphine, allowing prolonged oral fluid exposure to buprenorphine. Lastly, buprenorphine and its metabolites contributed to the biofilm formation of S. mutans in high concentration.

Conclusions: Sublingual administration substantially increased the salivary gland distribution of buprenorphine and norbuprenorphine. Depot effects following sublingual dosing and salivary gland accumulation likely sustained high oral fluid exposure to buprenorphine and stimulated the biofilm formation of S. mutans.

Keywords

Animals, Biofilms, Streptococcus mutans, Rats, Buprenorphine, Female, Salivary Glands, Rats, Inbred F344, Saliva, Administration, Sublingual, Dental Caries, Buprenorphine, Dental caries, Pharmacokinetics, Salivary gland, Oral fluid exposure

Published Open-Access

yes

Included in

Dentistry Commons

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