1. Norbuprenorphine and respiratory depression: Exploratory analyses with new lyophilized buprenorphine and sublingual buprenorphine .
- Author
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Strang J, Knight A, Baillie S, Reed K, Bogdanowicz K, and Bell J
- Subjects
- Administration, Sublingual, Analgesics, Opioid administration & dosage, Analgesics, Opioid blood, Analgesics, Opioid chemistry, Biological Availability, Biotransformation, Buprenorphine administration & dosage, Buprenorphine blood, Buprenorphine chemistry, Drug Compounding, Freeze Drying, Humans, Lung physiopathology, Opioid-Related Disorders blood, Opioid-Related Disorders diagnosis, Respiratory Insufficiency diagnosis, Respiratory Insufficiency physiopathology, Risk Factors, Solubility, Tablets, Treatment Outcome, Analgesics, Opioid adverse effects, Buprenorphine adverse effects, Buprenorphine analogs & derivatives, Lung drug effects, Opiate Substitution Treatment adverse effects, Opioid-Related Disorders drug therapy, Respiration drug effects, Respiratory Insufficiency chemically induced
- Abstract
Objectives: To investigate plasma levels of buprenorphine and norbuprenorphine and their relationship to respiratory depression., Materials and Methods: Opioid-dependent subjects were randomized 2 : 1 to novel lyophilized rapid-disintegrating tablet ("bup-lyo") or standard sublingual buprenorphine tablet ("bup-SL"). Measurements included oximetry scores and linked plasma buprenorphine and norbuprenorphine levels., Results: Respiratory depression (cumulative duration of SpO
2 < 90% over 30-minute periods) increased with corresponding exposure levels (AUC30 min ) of buprenorphine and particularly with norbuprenorphine. A lower buprenorphine/norbuprenorphine ratio was predictive of respiratory depression. The mean (SD) observed ratio was significantly higher for "bup-lyo" (3.4 (2.8)) compared to "bup-SL" (1.7 (0.77)), p < 0.0001., Conclusion: Exploratory investigation found respiratory depression more strongly associated with norbuprenorphine than with buprenorphine. This accords with animal studies. .- Published
- 2018
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