Buprenorphine not detected on urine drug screening in supervised treatment

Nazila Jamshidi, MBBS, FRACP, FAChAM, BPharm (hons), PhD; Akshay Athavale, MBBS, FRACP, BPharm (hons), MMed; Bridin Murnion, MBChB, FRACP, FFPMANZCA, FAChAM

doi:10.5055/jom.2021.0644

Authors

Nazila Jamshidi, MBBS, FRACP, FAChAM, BPharm (hons), PhD https://orcid.org/0000-0002-6049-9654
Akshay Athavale, MBBS, FRACP, BPharm (hons), MMed https://orcid.org/0000-0002-1649-8101
Bridin Murnion, MBChB, FRACP, FFPMANZCA, FAChAM

DOI:

https://doi.org/10.5055/jom.2021.0644

Keywords:

urine drug screen, buprenorphine, norbuprenorphine, detection rates

Abstract

Introduction: Urine drug screens (UDS) assist in clinical planning and assessment of adherence in opioid agonist treatment (OAT). Urine drug screens may also be used in criminal justice and child protection settings. Buprenorphine (BPN) UDS testing is complex. Immunoassay often does not detect BPN and gas chromatography-mass spectrometry (GC-MS) is needed. A limited understanding of testing can negatively influence UDS interpretation and clinical decision making.

Objectives: The primary aim was to determine detection rates of BPN in UDS in participants on BPN or buprenorphine/naloxone (BNX) treatment. The secondary aim was to identify if comorbidities, sex, co-prescribed medications, or dosing site and observation were associated with BPN detection.

Setting: Public outpatient clinic in a specialist addiction treatment service.

Design/participants: In this retrospective observational study, records of clients on supervised BPN/BNX treatment between September 2017 and 2018 were reviewed.

Measures: Data extracted included UDS results, age, sex, indication for BPN, frequency of observed doses, dose of BPN, dosing site, co-morbid medical conditions, and medications.

Results: One hundred and sixty-one medical records were reviewed. Ninety-seven (60 percent) underwent screening urine immunoassay. Of these 97, 51 (53 percent) had further GC-MS testing for BPN of which 22 (43 percent) did not detect BPN despite directly observed OAT. Co-prescription of medications known to interact with cytochrome P450 3A4 was associated with nondetection of BPN (p < 0.05). No significant association between median dose, dosing site, and observed dosing and BPN detection was identified.

Conclusion: Urine drug testing for BPN is complex. Failure to detect BPN does not betoken nonadherence to treatment and is associated with co-prescription of drugs interacting with cytochrome P450 3A4.

Author Biographies

Nazila Jamshidi, MBBS, FRACP, FAChAM, BPharm (hons), PhD

Drug Health Services, Sydney Local Health District, Sydney, New South Wales, Australia

Akshay Athavale, MBBS, FRACP, BPharm (hons), MMed

Drug Health Services, Sydney Local Health District, Sydney, New South Wales, Australia; Concord Clinical School, Faculty of Medicine and Health, University of Sydney, Camperdown, New South Wales, Australia

Bridin Murnion, MBChB, FRACP, FFPMANZCA, FAChAM

Faculty of Medicine and Health, University of Sydney, New South Wales, Australia; School of Medicine and Public Health, University of Newcastle, New South Wales, Australia; Drug Health Services, Central Coast Local Health District, Gosford, New South Wales, Australia

References

Health NSW: NSW clinical guidelines: Treatment of opioid dependence—2018. Sydney, 2018. https://www1.health.nsw.gov.au/pds/ActivePDSDocuments/GL2018_019.pdf. Accessed October 24, 2018.

Sordo L, Barrio G, Bravo MJ, et al.: Mortality risk during and after opioid substitution treatment: Systematic review and meta-analysis of cohort studies. BMJ. 2017; 357: j1550.

Kapuganti A, Turner T, Thomas CJ: Evaluation of buprenorphine/naloxone dose and use of sedating supportive medication on treatment outcomes in veterans with opioid use disorder. Ment Heal Clin. 2017; 7(6): 271-175.

Ronquest N, Willson T, Montejano L, et al.: Relationship between buprenorphine adherence and relapse, health care utilization and costs in privately and publicly insured patients with opioid use disorder. Subst Abuse Rehabil. 2018; 9: 59-78.

Samples H, Williams AR, Olfson M, et al.: Risk factors for discontinuation of buprenorphine treatment for opioid use disorders in a multi-state sample of Medicaid enrollees. J Subst Abuse Treat. 2018; 95: 9-17.

Moeller KE, Lee KC, Kissack JC: Urine drug screening: Practical guide for clinicians. Mayo Clin Proc. 2008; 83(1): 66-76.

Snyder ML, Fantz CR, Melanson S: Immunoassay-based drug tests are inadequately sensitive for medication compliance monitoring in patients treated for chronic pain. Pain Physician. 2017; 20(2): SE1-SE9.

Wood E, Mattick RP, Burns L, et al.: The costs and utility of parental drug-testing in child protection: A review of the available literature and commentary. NDRAC Technical Report No. 242, 2006.

Christo PJ, Manchikanti L, Ruan X, et al.: Urine drug testing in chronic pain. Pain Physician. 2011; 14(2): 123-143.

Petrides A, Melanson S: Urine drug testing|AACC.org. American Association for Clinical Chemistry. Available at https://www.aacc.org/publications/cln/articles/2019/janfeb/urinedrug-testing-debates-over-best-practices-to-assess-complianceand-manage-the-opioid-crisis. Published January 1, 2019. Accessed September 18, 2020.

Milone MC: Laboratory testing for prescription opioids. J Med Toxicol. 2012; 8(4): 408-416.

Elkader A, Sproule B: Buprenorphine: Clinical pharmacokinetics in the treatment of opioid dependence. Clin Pharmacokinet. 2005; 44(7): 661-680.

Cone EJ, Gorodetzky CW, Yousefnejad D, et al.: The metabolism and excretion of buprenorphine in humans. Drug Metab Dispos. 1984; 12(5): 577 LP-81.

Chang Y, Moody DE, McCance-Katz EF: Novel metabolites of buprenorphine detected in human liver microsomes and human urine. Drug Metab Dispos. 2006; 34(3): 440-448.

Kobayashi K, Yamamoto T, Chiba K, et al.: Human buprenorphine N-dealkylation is catalyzed by cytochrome P450 3A4. Drug Metab Dispos. 1998; 26(8): 818-821.

Moody DE, Fang WB, Morrison J, et al.: Gender differences in pharmacokinetics of maintenance dosed buprenorphine. Drug Alcohol Depend. 2011; 118(2-3): 479-483.

Böttcher M, Beck O: Evaluation of buprenorphine CEDIA assay versus GC-MS and ELISA using urine samples from patients in substitution treatment. J Anal Toxicol. 2005; 29(8): 769-776.

Schmidt RL, Panlener JJ, Carasso SM, et al.: Impact of continuous improvement of laboratory test result comments on requests for consultation: A case series. Am J Clin Pathol. 2016; 145(5): 666-670.

Khidr HI, Tegin C: Strategies for preventing and detecting false-negatives in urine drug screens. Curr Psychiatr. 2017; 16(1): e1-e3.

Holt SR, Donroe JH, Cavallo DA, et al.: Addressing discordant quantitative urine buprenorphine and norbuprenorphine levels: Case examples in opioid use disorder. Drug Alcohol Depend. 2018; 186(October 2017): 171-174.

Donroe JH, Holt SR, O’Connor PG, et al.: Interpreting quantitative urine buprenorphine and norbuprenorphine levels in office-based clinical practice. Drug Alcohol Depend. 2017; 180: 46-51.

Zanger UM, Schwab M: Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013; 138(1): 103-141.

Rouguieg K, Picard N, Sauvage F-L, et al.: Contribution of the different UDP-glucuronosyltransferase (UGT) isoforms to buprenorphine and norbuprenorphine metabolism and relationship with the main UGT polymorphisms in a bank of human liver microsomes. Drug Metab Dispos. 2010; 38(1): 40-45.

Schwarz DA, George MP, Bluth MH: Precision medicine in toxicology. Clin Lab Med. 2016; 36(4): 693-707.

Fazio SD, Gallelli L, Siena AD, et al.: Role of CYP3A5 in abnormal clearance of methadone. Ann Pharmacother. 2008; 42(6): 893-897.

Wojnowski L: Genetics of the variable expression of CYP3A in humans. Ther Drug Monit. 2004; 26(2): 192-199.

Lamba JK, Lin YS, Schuetz EG: Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev. 2012; 64: 256-269.

Strain EC, Moody DE, Stoller KB, et al.: Relative bioavailability of different buprenorphine formulations under chronic dosing conditions. Drug Alcohol Depend. 2004; 74(1): 37-43.

Unger A, Jung E, Winklbaur B, et al.: Gender issues in the pharmacotherapy of opioid-addicted women: Buprenorphine. J Addict Dis. 2010; 29(2): 217-230.

Abraham A, Luty J: Testing for illicit drug use in mental health services. Adv Psychiatr Treat. 2010; 16(5): 369-379.

Kronstrand R, Nyström I, Andersson M, et al.: Urinary detection times and metabolite/parent compound ratios after a single dose of buprenorphine. J Anal Toxicol. 2008; 32(8): 586-593.

McCance-Katz EF, Sullivan LE, Nallani S: Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: A review. Am J Addict. 2010; 19(1): 4-16.

Brown SM, Holtzman M, Kim T, et al.: Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active. Anesthesiology. 2011; 115(6): 1251-1260.

Hull MJ, Bierer MF, Griggs DA, et al.: Urinary buprenorphine concentrations in patients treated with Suboxone® as determined by liquid chromatography-mass spectrometry and CEDIA immunoassay. J Anal Toxicol. 2008; 32(7): 516-521.

Dickerson JA, Laha TJ, Pagano MB, et al.: Improved detection of opioid use in chronic pain patients through monitoring of opioid glucuronides in urine. J Anal Toxicol. 2012; 36(8): 541-547.

Pesce A, West C, Egan City K, et al.: Interpretation of urine drug testing in pain patients. Pain Med. 2012; 13(7): 868-885.