ArticlePharmaceutical research2008
Pharmacokinetic-pharmacodynamic modeling of the effectiveness and safety of buprenorphine and fentanyl in rats.
Article in Pharmaceutical research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Strategy for effective analgesia with intravenous buprenorphine in patients with acute postoperative pain.BMC anesthesiology · 2025Pooled it
- Buprenorphine for Chronic Pain: a Systemic Review.Current pain and headache reports · 2018Pooled it
- Pharmacokinetics of a Single Subcutaneous Extended-Release Buprenorphine (Ethiqa XR) in Healthy Beagles.Journal of veterinary pharmacology and therapeutics · 2026Article
- Pharmacokinetics of repeated, high-dose fentanyl administration in rats.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Evaluation of a human slow-release buprenorphine formulation in rats - tactile sensitivity and plasma concentration.Laboratory animal research · 2026Article
- Buprenorphine Pharmacodynamics: A Bridge to Understanding Buprenorphine Clinical Benefits.Drugs · 2025Review
- Respiratory Depression Associated with Opioids: A Narrative Review.Current treatment options in oncology · 2024Review
- Collateral Damage: Neurological Correlates of Non-Fatal Overdose in the Era of Fentanyl-Xylazine.Neuroscience insights · 2024Article
- Long-Acting Opioid Analgesics for Acute Pain: Pharmacokinetic Evidence Reviewed.Veterinary sciences · 2023Review
- Predicting transdermal fentanyl delivery using physics-based simulations for tailored therapy based on the age.Drug delivery · 2022Article
- Respiratory depression and analgesia by opioid drugs in freely behaving larval zebrafish.eLife · 2021Article
- Article
- Automated Classification of Whole Body Plethysmography Waveforms to Quantify Breathing Patterns.Frontiers in physiology · 2021Article
- Effects of Standard and Sustained-release Buprenorphine on the Minimum Alveolar Concentration of Isoflurane in C57BL/6 Mice.Journal of the American Association for Laboratory Animal Science : JAALAS · 2020Article
- Comparison of Postoperative Analgesic Effects Between Nalbuphine and Fentanyl in Children Undergoing Adenotonsillectomy: A Prospective, Randomized, Double-Blind, Multicenter Study.Frontiers in pharmacology · 2020Article
- Previously published drug interaction models predict loss of response for transoesophageal echocardiography sedation well but not response to oesophageal instrumentation.Scientific reports · 2019Article
- μ-Opioid Receptor Agonists: Do They Have Utility in the Treatment of Acute Pain?Anesthesiology · 2018Article
- Lack of adverse effects during a target animal safety trial of extended-release buprenorphine in Fischer 344 rats.Lab animal · 2016Article
- Kinetics of drug action in disease states: towards physiology-based pharmacodynamic (PBPD) models.Journal of pharmacokinetics and pharmacodynamics · 2015Article
- Buprenorphine - an attractive opioid with underutilized potential in treatment of chronic pain.Journal of pain research · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveRespiratory depression is a serious and potentially life-threatening side-effect of opioid therapy. The objective of this investigation was to characterize the relationship between buprenorphine or fentanyl exposure and the effectiveness and safety outcome in rats.
methodsData on the time course of the antinociceptive and respiratory depressant effect were analyzed on the basis of population logistic regression PK-PD models using non-linear mixed effects modeling software (NONMEM). The pharmacokinetics of buprenorphine and fentanyl were described by a three- and two-compartment model, respectively. A logistic regression model (linear logit model) was used to characterize the relationship between drug exposure and the binary effectiveness and safety outcome.
resultsFor buprenorphine, the odds ratios (OR) were 28.5 (95% CI, 6.9-50.1) and 2.10 (95% CI, 0.71-3.49) for the antinociceptive and respiratory depressant effect, respectively. For fentanyl these odds ratios were 3.03 (95% CI, 1.87-4.21) and 2.54 (95% CI, 1.26-3.82), respectively.
conclusionThe calculated safety index (OR(antinociception)/OR(respiratory depression)) for fentanyl of 1.20 suggests that fentanyl has a low safety margin, implicating that fentanyl needs to be titrated with caution. For buprenorphine the safety index is 13.54 suggesting that buprenorphine is a relatively safe opioid.
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Registered trials
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.