Buprenorphine / Norbuprenorphine

Common/Brand Names
Suboxone, Butrans, Subutex, Buprenex, Bunavail, Temgesic
Expected Screen Results
Buprenorphine
Expected Confirmation Results
Buprenorphine / Norbuprenorphine
Confirmation Cutoff
3/10
ng/mL
Detection Time
Up to
7
Days
Notes
Pharmacokinetic interactions may result when co-administered with CYP3A4 inhibitors
drug image

INTRODUCTION

Buprenorphine, a Schedule III – V (depending on the formulation) narcotic,is a semi-synthetic opiate derived from thebaine and is part of the phenanthrenes group1. This drug is an analgesic with mixed agonist-antagonist properties that is 20-40 times more potent than morphine and is utilized as a treatment for opioid dependence1,2. It is prescribed under the following trade names: Bunavail, Buprenex, Butrans, Suboxone, and Zubsolv. Buprenorphine is highly prescribed throughout the United States with 9.3 million being dispensed in 2012 and 2.5 million in the first quarter of 20133.   

PHARMACOLOGY                                            

ADMINISTRATION:

Buprenorphine is administered orally via a buccal film and a sublingual film/tablet with dosage ranges of 2.1-6.3 or 0.5-12 mg, respectively. It is also available in an extended release formulation via a transdermal patch with a dose of 5-20 µg/hr and a parenteral injection is obtainable with a usual dose of 0.3 mg. Naloxone is commonly combined with buprenorphine in order to minimize abuse potential2.  

DISTRIBUTION:

Following a 2 mg sublingual dose, the average peak plasma concentration occurred at 1.3 hrs with a half-life of 18-49 hrs. A 0.3 mg intravenous dose resulted in an average peak plasma concentration at 2 minutes with a half-life of 2-4 hrs2.   The bioavailability is approximately 51% via sublingual administration or 28% via a buccal film5.

METABOLISM:

Buprenorphine is primarily N-dealkylated by CYP3A4 in order to form the pharmacology active norbuprenorphine in which both undergo conjugation2.

EXCRETION:

Within 6-11 days, approximately 95% of a dose is eliminated with around 68% excreted in the feces and 27% in the urine. In urine, the majority of the drug is excreted as buprenorphine glucuronide and norbuprenorphine glucuronide at 9.4% and 11%, respectively2,4. 

METHODS OF ANALYSIS

A highly specific buprenorphine Enzyme Immunoassay (EIA) screening methodology is utilized for the detection of buprenorphine and norbuprenorphine with a cutoff concentration of 5 ng/mL. Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) is used to confirm and quantify buprenorphine and norbuprenorphine, with a cutoff concentration of 3 ng/mL and 10 ng/mL, respectively. The urine samples are hydrolyzed prior to analysis and total buprenorphine and norbuprenorphine concentrations are reported.

INTERPRETATION

Patients prescribed buprenorphine should contain both buprenorphine and norbuprenorphine in the urine. In a study conducted by McMillen et al., out of 1,946 positive buprenorphine samples, 94.45% contained buprenorphine and norbuprenorphine, 4.87% had only norbuprenorphine present, and 0.67% contained only parent drug6. If buprenorphine is in high concentrations in the urine without the presence of norbuprenorphine, the possibility of patient tampering should be considered; however, patients co-administered CYP3A4 inhibitors may have lower than expected concentrations of norbuprenorphine.

References

  1. Ropero-Miller. J.D., Goldberger.B.A (2001) Opioids. In Shaw.L.M. (eds). The Clinical Toxicology Laboratory Contemporary Practice of Poisoning Evaluation, Chapter 6. AACC Press. Washington, D.C., 73-95.
  2. Baselt, R. C. (2011) Disposition of Toxic Drugs and Chemicals in Man, 9th Edition. Biomedical Publications, Seal Beach, CA, 818-820.
  3. Drug Enforcement Administration. (2013) Buprenorphine. Retrieved from deadivision.gov. http://www.deadiversion.usdoj.gov/drug_chem_info/buprenorphine.pdf.
  4. Food and Drug Administration (2011) Suboxone (Reference ID 3063079) Retrieved from fda.gov. http://www.accessdata.fda.gov/drugsatfdalabel/2011/020733s007s008lbl.pdf
  5. Kuhlman, J.J., Lalani. S., Magluilo, J., Levine, B. , Darwin, W.D., Johnson, R.E., Cone, E.J., (1996) Human Pharmacokinetics of Intraveneous, Sublingual and Buccal Buprenorphine. Jouranl of Analytical Toxicology, 20, 369-378
  6. McMillen, G.A., Davis, R., Carlisle, H., Clark, C., Marin, S.J., and Moody, D., (2012) Patterns of Free (Unconjugated) Buprenorphine, Norbuprenorphine, and Their Glucuronides in Urine Using Liquid Chromatography-Tandem Mass Spectrometry.  Journal of Analytical Toxicology, 36, 81-87.