Abstract | BACKGROUND: METHODS: In this two-period crossover, single-centre study, 14 healthy volunteers (single-blind, randomized) and eight opioid-tolerant patients taking daily opioid doses ≥90 mg oral morphine equivalents (open-label) received continuous intravenous buprenorphine or placebo for 360 minutes, targeting buprenorphine plasma concentrations of 0.2 or 0.5 ng/mL in healthy volunteers and 1.0, 2.0 or 5.0 ng/mL in opioid-tolerant patients. Upon reaching target concentrations, participants received up to four escalating intravenous doses of fentanyl. The primary endpoint was change in isohypercapnic minute ventilation (VE). Additionally, occurrence of apnea was recorded. RESULTS:
Fentanyl-induced changes in VE were smaller at higher buprenorphine plasma concentrations. In healthy volunteers, at target buprenorphine concentration of 0.5 ng/mL, the first and second fentanyl boluses reduced VE by [LSmean (95% CI)] 26% (13-40%) and 47% (37-59%) compared to 51% (38-64%) and 79% (69-89%) during placebo infusion (p = 0.001 and < .001, respectively). Discontinuations for apnea limited treatment comparisons beyond the second fentanyl injection. In opioid-tolerant patients, fentanyl reduced VE up to 49% (21-76%) during buprenorphine infusion (all concentration groups combined) versus up to 100% (68-132%) during placebo infusion (p = 0.006). In opioid-tolerant patients, the risk of experiencing apnea requiring verbal stimulation following fentanyl boluses was lower with buprenorphine than with placebo (odds ratio: 0.07; 95% CI: 0.0 to 0.3; p = 0.001). INTERPRETATION:
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Authors | Laurence M Moss, Marijke Hyke Algera, Robert Dobbins, Frank Gray, Stephanie Strafford, Amy Heath, Monique van Velzen, Jules A A C Heuberger, Marieke Niesters, Erik Olofsen, Celine M Laffont, Albert Dahan, Geert Jan Groeneveld |
Journal | PloS one
(PLoS One)
Vol. 17
Issue 1
Pg. e0256752
( 2022)
ISSN: 1932-6203 [Electronic] United States |
PMID | 35085249
(Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Delayed-Action Preparations
- Buprenorphine
- Fentanyl
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Topics |
- Adult
- Buprenorphine
(administration & dosage, pharmacokinetics)
- Cross-Over Studies
- Delayed-Action Preparations
- Female
- Fentanyl
(adverse effects)
- Healthy Volunteers
- Humans
- Infusions, Intravenous
- Male
- Middle Aged
- Opioid-Related Disorders
(blood, drug therapy)
- Proof of Concept Study
- Respiratory Insufficiency
(blood, chemically induced, drug therapy)
- Single-Blind Method
- Young Adult
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