ArticleAnesthesiology2011
Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active.
Article in Anesthesiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 163 citations in OpenAlex.
- Tapentadol, Buprenorphine, and Levorphanol for the Treatment of Neuropathic Pain: a Systematic Review.Current pain and headache reports · 2021Pooled it
- Voriconazole greatly increases the exposure to oral buprenorphine.European journal of clinical pharmacology · 2018Trial
- Voriconazole more likely than posaconazole increases plasma exposure to sublingual buprenorphine causing a risk of a clinically important interaction.European journal of clinical pharmacology · 2016Trial
- The Buprenorphine Paradox: How Buprenorphine Triggers and Resolves Opioid Withdrawal.Addiction biology · 2026Article
- An Experimental Study to Evaluate the Role of Buprenorphine, Morphine, and Naltrexone in Animal Models of Depression.Cureus · 2025Article
- Pharmacogenetic exploration of buprenorphine and related metabolites in umbilical cord blood.Toxicology reports · 2025Article
- Antidepressants and the endogenous opioid system.Biochemical pharmacology · 2025Review
- Pharmacokinetic Analysis of Sustained-Release Buprenorphine Formulations in Owl Monkeys (Aotus spp.).Journal of the American Association for Laboratory Animal Science : JAALAS · 2025Article
- Evaluation of Extended- and Immediate-Release Buprenorphine Formulations on Pharmacokinetics and Injection Site Lesions in Different Strains and Sex of Mice.Journal of the American Association for Laboratory Animal Science : JAALAS · 2025Article
- Expanding Horizons of Buprenorphine: A Comprehensive Narrative Review of Its Pharmacological Properties and Clinical Applications in Chronic Pain.Pain and therapy · 2025Review
- Article
- Opioid metabolism and drug-drug interaction in cancer.The oncologist · 2024Review
- Evaluation of the Hepatotoxicity of Buprenorphine in Rat Pups Born to an Exposed Mother During Lactation.Cardiovascular & hematological agents in medicinal chemistry · 2024Article
- Reconsidering the usefulness of long-term high-dose buprenorphine.Frontiers in psychiatry · 2024Article
- Plasma concentrations of buprenorphine administered via matrix-type transdermal patches applied at three different anatomical locations in healthy adult horses.Frontiers in pain research (Lausanne, Switzerland) · 2024Article
- Nalmefene Hydrochloride: Potential Implications for Treating Alcohol and Opioid Use Disorder.Substance abuse and rehabilitation · 2024Review
- Evaluation of physical variables, thermal nociceptive threshold testing and pharmacokinetics during placement of transdermal buprenorphine matrix-type patch in healthy adult horses.Frontiers in pain research (Lausanne, Switzerland) · 2024Article
- An Examination of the Complex Pharmacological Properties of the Non-Selective Opioid Modulator Buprenorphine.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Pharmacological Treatments and Therapeutic Drug Monitoring in Patients with Chronic Pain.Pharmaceutics · 2023Review
- Interaction between buprenorphine and norbuprenorphine in neonatal opioid withdrawal syndrome.Drug and alcohol dependence · 2023Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe long-lasting high-affinity opioid buprenorphine has complex pharmacology, including ceiling effects with respect to analgesia and respiratory depression. Plasma concentrations of the major buprenorphine metabolites norbuprenorphine, buprenorphine-3-glucuronide, and norbuprenorphine-3-glucuronide approximate or exceed those of the parent drug. Buprenorphine glucuronide metabolites pharmacology is undefined. This investigation determined binding and pharmacologic activity of the two glucuronide metabolites, and in comparison with buprenorphine and norbuprenorphine.
methodsCompetitive inhibition of radioligand binding to human μ, κ, and δ opioid and nociceptin receptors was used to determine glucuronide binding affinities for these receptors. Common opiate effects were assessed in vivo in SwissWebster mice. Antinociception was assessed using a tail-flick assay, respiratory effects were measured using unrestrained whole-body plethysmography, and sedation was assessed by inhibition of locomotion measured by open-field testing.
resultsBuprenorphine-3-glucuronide had high affinity for human μ (Ki [inhibition constant] = 4.9 ± 2.7 pM), δ (Ki = 270 ± 0.4 nM), and nociceptin (Ki = 36 ± 0.3 μM) but not κ receptors. Norbuprenorphine-3-glucuronide had affinity for human κ (Ki = 300 ± 0.5 nM) and nociceptin (Ki = 18 ± 0.2 μM) but not μ or δ receptors. At the dose tested, buprenorphine-3-glucuronide had a small antinociceptive effect. Neither glucuronide had significant effects on respiratory rate, but norbuprenorphine-3-glucuronide decreased tidal volume. Norbuprenorphine-3-glucuronide also caused sedation.
conclusionsBoth glucuronide metabolites of buprenorphine are biologically active at doses relevant to metabolite exposures, which occur after buprenorphine. Activity of the glucuronides may contribute to the overall pharmacology of buprenorphine.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.