Norbuprenorphine and respiratory depression: Exploratory analyses with new lyophilized buprenorphine and sublingual buprenorphine
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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 SpO2 < 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.
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• Authors: John Strang, Alastair Knight, Shelagh Baillie, Kylie Reed, Karolina Bogdanowicz, James Bell
• Journal: International journal of clinical pharmacology and therapeutics (Int J Clin Pharmacol Ther) Vol. 56 Issue 2 Pg. 81-85 (Feb 2018) ISSN: 0946-1965 [Print] Germany
• PMID: 29231163 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Analgesics, Opioid
• Tablets
• Buprenorphine
• norbuprenorphine

Topics

• Administration, Sublingual
• Analgesics, Opioid (administration & dosage, adverse effects, blood, chemistry)
• Biological Availability
• Biotransformation
• Buprenorphine (administration & dosage, adverse effects, analogs & derivatives, blood, chemistry)
• Drug Compounding
• Freeze Drying
• Humans
• Lung (drug effects, physiopathology)
• Opiate Substitution Treatment (adverse effects)
• Opioid-Related Disorders (blood, diagnosis, drug therapy)
• Respiration (drug effects)
• Respiratory Insufficiency (chemically induced, diagnosis, physiopathology)
• Risk Factors
• Solubility
• Tablets
• Treatment Outcome