Buprenorphine Salivary Gland Accumulation Sustaining High Oral Fluid Exposure and Increasing the Risk of Streptococcus mutans Biofilm Formation.

IF 4.2 3区医学 Q1 SUBSTANCE ABUSE Journal of Addiction Medicine Pub Date : 2024-12-02 DOI:10.1097/ADM.0000000000001401

Zicong Zheng, Jie Chen, Songpol Srinual, Vesna Tumbas Šaponjac, Taijun Yin, Bing-Yan Wang, Rongjin Sun, Ming Hu

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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.

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丁丙诺啡唾液腺积聚维持高口服液暴露和增加变形链球菌生物膜形成的风险。

目的：美国食品和药物管理局（FDA）于2022年发布了关于丁丙诺啡致未知机制龋齿的警告。为了研究潜在的机制，本研究将探讨局部丁丙诺啡暴露与牙齿生物膜形成之间的关系。方法：雌性F344大鼠舌下注射丁丙诺啡膜或静脉注射丁丙诺啡，探讨丁丙诺啡口腔暴露情况。舌下和静脉给药后丁丙诺啡在唾液腺中的分布也进行了评估。为了探讨丁丙诺啡暴露对龋形成的影响，我们在体外测定了丁丙诺啡对变形链球菌生物膜形成的影响。结果：丁丙诺啡在大鼠的绝对舌下生物利用度为17.8%，口服液暴露与血药浓度之比较高。丁丙诺啡及其活性代谢物去甲丁丙诺啡的唾液腺浓度显著高于舌下（s.l）和静脉（i.v）给药后的血液浓度。相关分析显示，丁丙诺啡和去甲丁丙诺啡口服液浓度与唾液腺浓度高度相关，而与血药浓度无关。这些数据表明唾液腺是丁丙诺啡的蓄积器官，允许长期的口服液暴露于丁丙诺啡。最后，丁丙诺啡及其代谢物在高浓度下对变形链球菌的生物膜形成有促进作用。结论：舌下给药显著增加了丁丙诺啡和去甲丁丙诺啡的唾液腺分布。舌下剂量和唾液腺积聚后的储存效应可能持续高剂量的口服液暴露于丁丙诺啡并刺激变形链球菌的生物膜形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Addiction Medicine 医学-药物滥用

CiteScore

6.10

自引率

9.10%

发文量

260

审稿时长

>12 weeks

期刊介绍： The mission of Journal of Addiction Medicine, the official peer-reviewed journal of the American Society of Addiction Medicine, is to promote excellence in the practice of addiction medicine and in clinical research as well as to support Addiction Medicine as a mainstream medical sub-specialty. Under the guidance of an esteemed Editorial Board, peer-reviewed articles published in the Journal focus on developments in addiction medicine as well as on treatment innovations and ethical, economic, forensic, and social topics including: •addiction and substance use in pregnancy •adolescent addiction and at-risk use •the drug-exposed neonate •pharmacology •all psychoactive substances relevant to addiction, including alcohol, nicotine, caffeine, marijuana, opioids, stimulants and other prescription and illicit substances •diagnosis •neuroimaging techniques •treatment of special populations •treatment, early intervention and prevention of alcohol and drug use disorders •methodological issues in addiction research •pain and addiction, prescription drug use disorder •co-occurring addiction, medical and psychiatric disorders •pathological gambling disorder, sexual and other behavioral addictions •pathophysiology of addiction •behavioral and pharmacological treatments •issues in graduate medical education •recovery •health services delivery •ethical, legal and liability issues in addiction medicine practice •drug testing •self- and mutual-help.