Norbuprenorphine is a major metabolite of buprenorphine and potent agonist of μ, δ, and κ opioid receptors. Compared with buprenorphine, norbuprenorphine causes minimal antinociception but greater respiratory depression. It is unknown whether the limited antinociception is caused by low efficacy or limited brain exposure. Norbuprenorphine is an in vitro substrate of the efflux transporter P-gly...

The objective of this investigation was to characterize the pharmacokinetic-pharmacodynamic (PK-PD) correlation of buprenorphine's active metabolite norbuprenorphine for the effect on respiration in rats. Following i.v. administration in rats (dose range 0.32-1.848 mg), the time course of the concentration in plasma was determined in conjunction with the effect in ventilation as determined with...

BACKGROUND The 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...

A method for the simultaneous measurement of buprenorphine and its N-dealkylated metabolite, norbuprenorphine, in human plasma was developed with negative chemical ionization tandem mass spectrometry. Buprenorphine and norbuprenorphine were extracted from biological fluids by solid-phase extraction. The samples were derivatized with heptafluorobutyric anhydride and measured with negative chemic...

OBJECTIVE The aim of the present study was to estimate the dose of buprenorphine and its primary metabolite norbuprenorphine that a breastfed infant would receive during maternal maintenance treatment with buprenorphine. STUDY DESIGN Seven pregnant opioid-dependent women taking buprenorphine (median, 7 mg/day; range, 2.4-24 mg) and who intended to breastfeed were recruited. After lactation wa...

Buprenorphine and buprenorphine-naloxone fixed combinations are effective for managing patients with opioid dependence, but constipation is one of the most common side effects. Evidence indicates that the rate of constipation is lower when patients are switched from sublingual buprenorphine-naloxone tablets or films to a bilayered bioerodible mucoadhesive buccal film formulation, and while the ...

A sensitive, simple and rapid high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and fully validated for the simultaneous quantification of buprenorphine (BUP) and its N-dealkylated metabolite norbuprenorphine (NBUP) in 200 μL human plasma. Human plasma samples were prepared using liquid-liquid extraction, and then separated on a Shiseido MG C18 (5...

Buprenorphine is a strong narcotic analgesic. It is also used in the substitution therapy for opium alkaloid addicts. The aim of this paper was to develop and validate a highly sensitive high-performance liquid chromatography-electrospray ionization-mass spectrometry method for simultaneous determination of buprenorphine and norbuprenorphine in human serum. The developed methodology was then ap...

BACKGROUND Buprenorphine is under investigation as a pharmacotherapeutic agent for treating opioid dependence in pregnant women. We hypothesized that there would be a relationship between the cumulative maternal dose of buprenorphine during pregnancy and the concentration of buprenorphine and norbuprenorphine in maternal and infant hair. METHODS This study examined buprenorphine and norbupren...

We tested the hypothesis that primary cultures of human hepatocytes could predict potential drug interactions with methadone and buprenorphine. Hepatocytes (five donors) were preincubated with dimethyl sulfoxide (DMSO) (vehicle), rifampin, or nelfinavir before incubation with methadone or buprenorphine. Culture media (0-60 min) was analyzed by liquid chromatography-tandem mass spectrometry for ...