Buprenorphine blood concentrations: A biomarker for analgesia
DOI:
https://doi.org/10.5055/jom.2021.0638Keywords:
buprenorphine, biomarker, analgesia, acute pain, pharmacokineticsAbstract
Opioids, the frontline drugs for postsurgical analgesia, have been linked to diversion and abuse with lethal consequences. The search for safe analgesics with less harm potential has been decades long. However, clinical trials for safe opioid and nonopioid analgesics have relied on subjective pain reports, which are biased by placebo effects that increase the complexity of trials to develop new therapies to manage pain.
Research in opioid naïve animals and humans demonstrates that blood concentrations of opioids that effectively saturate the morphine opioid receptor are tightly linked with patient reports and quantitative sensory tests for analgesia. Opioid drug concentrations can predict clinical responses.
This report reviews preclinical and clinical evidence correlating buprenorphine pharmacokinetics with analgesia. More than 30 years of data confirm buprenorphine blood concentrations can be an objective biomarker of analgesia for moderate to severe acute postoperative pain.
References
Bicket MC, Long JJ, Pronovost PJ, et al.: Prescription opioid analgesics commonly unused after surgery. JAMA Surg. 2017; 152(11): 1066-1071. DOI: 10.1001/jamasurg.2017.0831.
Coe MA, Lofwall MR, Walsh SL: Buprenorphine pharmacology review: Update on transmucosal and long-acting formulations. J Addict Med. 2019; 13(2): 93-103.
Howick J, Webster R, Kirby N, et al.: Rapid overview of systematic reviews of nocebo effects reported by patients taking placebos in clinical trials. Trials. 2018; 19: 674. DOI: 10.1186/s13063-018-3042-4.
Kaminski J, Hynds J, Morris P, et al.: Human attention affects facial expressions in domestic dogs. Sci Rep. 2017; 197(1): 12914. DOI: 10.1038/s41598-017-12781-x.
Moran CE, Hofmeister EH: Prevalence of pain in a university veterinary intensive care unit. J Vet Emerg Crit Care (San Antonio). 2013; 23: 29-36.
Available at https://www.fda.gov/science-research/aboutscience-research-fda/biomarkers-fda. Accessed December 15, 2020.
Reckziegel D, Vachon-Presseau E, Petre B, et al.: Deconstructing biomarkers for chronic pain: Context- and hypothesis-dependent biomarker types in relation to chronic pain. Pain. 2019; 160(Suppl. 1): S37-S48. DOI: 10.1097/j.pain.0000000000001529.
Thudium CS, Löfvall H, Karsdal MA, et al.: Protein biomarkers associated with pain mechanisms in osteoarthritis. J Proteomics. 2019; 190: 55-66. DOI: 10.1016/j.jprot.2018.04.030.
Mouraux A, Iannetti GD: The search for pain biomarkers in the human brain. Brain. 2018; 141(12): 3290-3307. DOI: 10.1093/brain/awy281.
Serra R, Gorelick ML, Tyler BT, et al.: Brain imaging: A promising biomarker for pain. Biomed J Sci Tech Res. 2018; 6(3): 5347-5349. Available at https://biomedres.us/pdfs/BJSTR.MS.ID.001369.pdf. Accessed December 15, 2020.
Khan AN, Jacobsen HE, Khan J, et al.: Inflammatory biomarkers of low back pain and disc degeneration: A review. Ann NY Acad Sci. 2017; 1410(1): 68-84. DOI: 10.1111/nyas.13551.
Gunn J, Hill MM, Cotten BM, et al.: An analysis of biomarkers in patients with chronic pain. Pain Physician. 2020; 23(1): E41-E49.
Marchi A, Vellucci R, Mameli S, et al.: Pain biomarkers. Clin Drug Investig. 2009; 29(Suppl. 1): 41-46. DOI: 10.2165/0044011-200929001-00006.
Ye X, Itzoe M, Sarabia-Estrada R, et al.: Suspected lonely mouse syndrome as a cage effect in a drug safety study. J Vet Med. 2018; 2018: 1-5. DOI: 10.1155/2018/9562803.
Conzemius MG, Hill CM, Sammarco JL, et al.: Correlation between subjective and objective measures used to determine severity of postoperative pain in dogs. J Am Vet Med Assoc. 1998; 210: 1619-1623.
Plant JD: Repeatability and reproducibility of numerical rating scales and visual analogue scales for canine pruritus severity scoring. Vet Dermatol. 2007; 18(5): 294-300.
Chiarotto A, Maxwell LJ, Ostelo RW, et al.: Measurement properties of visual analogue scale, numeric rating scale and pain severity subscale of the brief pain inventory in patients with low back pain: A systematic review. Pain. 2019; 20(3): 245-263. DOI: 10.1016/j.jpain.2018.07.009.
Ramanathan S, Ajit SK: MicroRNA-based biomarkers in pain. Adv Pharmacol. 2016; 75: 35-62. DOI: 10.1016/bs.apha.2015.12.001.
Sisignano M, Lötsch J, Parnham MJ, et al.: Potential biomarkers for persistent and neuropathic pain therapy. Pharmacol Ther. 2019; 199: 16-29. DOI: 10.1016/j.pharmthera.2019.02.004.
Tracey I, Woolf CJ, Andrews NA: Composite pain biomarker signatures for objective assessment and effective treatment. Neuron. 2019; 101(5): 783-800. DOI: 10.1016/j.neuron.2019.02.019.
Pasternak GW: Mu opioid pharmacology: 40 years to the promised land. Adv Pharmacol. 2018; 82: 261-291.
Yassen A, Olofsen E, Kan J, et al.: Animal-to-human extrapolation of the pharmacokinetic and pharmacodynamic properties of buprenorphine. Clin Pharmacokinet. 2007; 46(5): 433-447.
Lutfy K, Cowan A: Buprenorphine: A unique drug with complex pharmacology. Curr Neuropharmacol. 2004; 2: 395-402.
Guarnieri M, Kedda J, Tyler B: Buprenorphine implants: “A model for expedited development and approval of new drugs”. Curr Med Res Opin. 2021; 37: 83-88. DOI: 10.1080/03007995.2020.1840971.
Davis MP, Pasternak G, Behm B: Treating chronic pain: An overview of clinical studies centered on the buprenorphine option. Drugs. 2018; 78(12): 1211-1228. DOI: 10.1007/s40265-018-0953-z.
Available at https://clinicaltrials.gov. Accessed December 15, 2020.
Harcus AH, Ward AE, Smith DW: Buprenorphine in postoperative pain: Results in 7500 patients. Anaesthesia. 1980; 35: 382-386.
Harcus AH, Ward AE, Smith DW: Buprenorphine: Experience in an elderly population of 975 patients during a year's monitored release. Br J Clin Pract. 1980; 34(5): 144-146.
Bullingham RE, McQuay HJ, Moore A, et al.: Buprenorphine kinetics. Clin Pharmacol Ther. 1980; 28(5): 667-672. DOI: 10.1038/clpt.1980.219.
Watson PJ, McQuay HJ, Bullingham RE, et al.: Single-dose comparison of buprenorphine 0.3 and 0.6 mg i.v. given after operation: Clinical effects and plasma concentration. Br J Anaesth. 1982; 54(1): 37-43.
Shah MV, Jones DI, Rosen M: Patient demand’ postoperative analgesia with buprenorphine: Comparison between sublingual and i.m. administration. Br J Anaesth. 1986; 58(5): 508-511. DOI: 10.1093/bja/58.5.508.
Kamel MM, Geddes IC: A comparison of buprenorphine and pethidine for immediate postoperative pain relief by the i.v. route. Br J Anaesth. 1978; 50(6): 599-603. DOI: 10.1093/bja/50.6.599.
Hayes MJ, Fraser AR, Hampton JR: Randomized trial comparing buprenorphine and diamorphine for chest pain in suspected myocardial infarction. Br Med J. 1979; 2(6185): 300-302. DOI: 10.1136/bmj.2.6185.300.
Donadoni R, Rolly G: Epidural sufentanil versus intramuscular buprenorphine for postoperative analgesia: A double-blind comparative trial. Anaesthesia. 1987; 42(11): 1171-1175. DOI: 10.1111/j.1365-2044.1987.tb05222.x.
Monk JP, Beresford R, Ward A: Sufentanil: A review of its pharmacological properties and therapeutic use. Drugs. 1988; 36(3): 286-313. DOI: 10.2165/00003495-198836030-00003.
Bilsback P, Rolly G, Tampubolon O: Efficacy of the extradural administration of lofentanil, buprenorphine or saline in the management of postoperative pain: A double-blind study. Br J Anaesth. 1985; 57(10): 943-948. DOI: 10.1093/bja/57.10.943.
Guarnieri M, Brayton C, DeTolla L, et al.: Safety and efficacy of buprenorphine for analgesia in laboratory mice and rats. Lab Anim. 2012; 41(11): 337-343.
Traul KA, Romero JB, Brayton C, et al.: Safety studies of postsurgical buprenorphine therapy for mice. Lab Anim. 2015; 49(2): 100-110.
Clark TS, Clark DD, Hoyt RF: Pharmacokinetic comparison of sustained release and standard buprenorphine in mice. J Am Assoc Lab Anim Sci. 2014; 53(4): 387-391.
Cowan A, Sarabia-Estrada R, Wilkerson G, et al.: Unanticipated adverse events associated with an extended-release buprenorphine toxicity study in Fischer 344 rats. Lab Anim. 2016; 45(1): 28-34.
Chum HH, Jampachairsri K, McKeon GP, et al.: Antinociceptive effects of sustained-release buprenorphine in a model of incisional pain in rats (Rattus norvegicus). J Am Assoc Lab Anim Sci. 2014; 53: 193-197.
DiVincenti L Jr, Meirelles LA, Westcott RA: Safety and clinical effectiveness of a compounded sustained-release formulation of buprenorphine for postoperative analgesia in New Zealand white rabbits. J Am Vet Med Assoc. 2016; 248(7): 795-801.
Oliver VL, Athavale S, Simon KE, et al.: Evaluation of pain assessment techniques and analgesia efficacy in a female Guinea pig (Cavia porcellus) model of surgical pain. J Am Assoc Lab Anim Sci. 2017; 56(4): 425-435.
Smith BJ, Wegenast DJ, Hansen RJ, et al.: Pharmacokinetics and paw withdrawal pressure in female Guinea pigs (Cavia porcellus) treated with sustained-release buprenorphine and buprenorphine hydrochloride. J Am Assoc Lab Anim Sci. 2016; 55(6): 789-793.
Cary CD, Lukovsky-Akhsanov NL, Gallardo-Romero NF, et al.: Pharmacokinetic profiles of meloxicam and sustained-release buprenorphine in prairie dogs (Cynomys ludovicianus). J Am Assoc Lab Anim Sci. 2017; 56(2): 160-165.
Sramek MK, Haas MC, Coleman GD, et al.: The safety of high-dose buprenorphine administered subcutaneously in cats. J Vet Pharmacol Therap. 2015; 38: 434-442. DOI: 10.1111/jvp.12203.
Barletta M, Ostenkamp SM, Taylor AC, et al.: The pharmacokinetics and analgesic effects of extended-release buprenorphine administered subcutaneously in healthy dogs. J Vet Pharmacol Ther. 2018; DOI: 10.1111/jvp.12497.
Nunamaker EA, Stolarik DF, Ma J, et al.: Clinical efficacy of sustained-release buprenorphine with meloxicam for postoperative analgesia in beagle dogs undergoing ovariohysterectomy. J Am Assoc Lab Anim Sci. 2014; 53(5): 494-501.
Thiede AJ, Garcia KD, Stolarik DF, et al.: Pharmacokinetics of sustained-release and transdermal buprenorphine in göttingen minipigs (Sus scrofa domestica). J Am Assoc Lab Anim Sci. 2014; 53(6): 692-699.
Walkowiak KJ, Graham ML: Pharmacokinetics and antinociceptive activity of sustained-release buprenorphine in sheep. J Am Assoc Lab Anim Sci. 2015; 54(6): 763-768.
Nunamaker EA, Halliday LC, Moody DE, et al.: Pharmacokinetics of 2 formulations of buprenorphine in macaques (Macaca mulatta and Macaca fascicularis). J Am Assoc Lab Anim Sci. 2013; 52: 48-56.
Bannon AW, Malmberg AB: Models of nociception: Hotplate, tail-flick, and formalin tests in rodents. Curr Protoc Neurosci. 2007; 41: 8.9.1-8.9.16.
Guarnieri M, Brayton C, Sarabia-Estrada R, et al.: Subcutaneous implants of a cholesterol-triglyceride-buprenorphine suspension in rats. J Vet Med. 2017; 2017: 1-11. DOI: 10.1155/2017/3102567.
Liu KS, Kao CH, Liu SY, et al.: Novel depots of buprenorphine have a long-acting effect for the management of physical dependence to morphine. J Pharm Pharmacol. 2006; 58(3): 337-344.
Foley PL: Current options for providing sustained analgesia to laboratory animals. Lab Anim. 2014; 43(10): 364-371.
Kleppner SR, Patel R, McDonough J, et al.: In-vitro and in-vivo characterization of a buprenorphine delivery system. J Pharm Pharmacol. 2006; 58(3): 295-302. DOI: 10.1211/jpp.58.3.0002.
Pieper K, Schuster T, Levionnois O, et al.: Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs. Vet J. 2011; 187(3): 335-341.
Park I, Kim D, Song J, et al.: Buprederm, a new transdermal delivery system of buprenorphine: Pharmacokinetic, efficacy and skin irritancy studies. Pharm Res. 2008; 25(5): 1052-1062.
Adriaensen H, Mattelaer B, Vanmeenen HA: Long-term open, clinical and pharmacokinetic assessment of sublingual buprenorphine in patients suffering from chronic pain. Acta Anaesthesiol Belg. 1985; 36(1): 33-40.
Brown SM, Holtzman M, Kim T, et al.: Buprenorphine metabolites, buprenorphine-3-glucuronide, and norbuprenorphine-3-glucuronide, are biologically active. Anesthesiology. 2011; 115: 1251-1260.
Snyder SH: Opiate receptors in the brain. N Engl J Med. 1977; 296(5): 266-271.
Raffa RB, Haidery M, Huang H-M, et al.: The clinical analgesic efficacy of buprenorphine. J Clin Pharm Ther. 2014; 39: 577-583. DOI: 10.1111/jcpt.12196.
Yassen A, Olofsen E, Kan J, et al.: Pharmacokineticpharmacodynamic modeling of the effectiveness and safety of buprenorphine and fentanyl in rats. Pharm Res. 2008; 25(1): 183-193.
Kalluri HV, Zhang H, Caritis SN, et al.: A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration. Br J Clin Pharmacol. 2017; 83: 2458-2473.
Ohtani M, Kotaki H, Sawada Y, et al.: Comparative analysis of buprenorphine- and norbuprenorphine-induced analgesic effects based on pharmacokinetic-pharmacodynamic modeling. J Pharmacol Exp Ther. 1995; 272(2): 505-510.
Walsh SL, Comer SD, Lofwall MR, et al.: Effect of buprenorphine weekly depot (CAM2038) and hydromorphone blockade in individuals with opioid use disorder: A randomized clinical trial. JAMA Psychiatry. 2017; 74: 894.
Nasser AF, Greenwald MK, Vince B, et al.: Sustained-release buprenorphine (RBP-6000) blocks the effects of opioid challenge with hydromorphone in subjects with opioid use disorder. J Clin Psychopharmacol. 2016; 36: 18-26.
Rosenthal RN, Ling W, Casadonte P, et al.: Buprenorphine implants for treatment of opioid dependence: Randomized comparison to placebo and sublingual buprenorphine/naloxone. Addiction. 2013; 108(12): 2141-2149.
Pergolizzi JV Jr, Raffa RB: Safety and efficacy of the unique opioid buprenorphine for the treatment of chronic pain. J Pain Res. 2019; 12: 3299-3317. DOI: 10.2147/JPR.S231948.
Davis MP: Twelve reasons for considering buprenorphine as a frontline analgesic in the management of pain. J Support Oncol. 2012; 10(6): 209-219. DOI: 10.1016/j.suponc.2012.05.002.
White LD, Hodge A, Vlok R, et al.: Efficacy and adverse effects of buprenorphine in acute pain management: Systematic review and meta-analysis of randomised controlled trials. Br J Anaesth. 2018; 120(4): 668-678. DOI: 10.1016/j.bja.2017.11.086.
Strain EC, Moody DE, Stoller KB, et al.: Relative bioavailability of different buprenorphine formulations under chronic dosing conditions. Drug Alcohol Depend. 2004; 74: 37-43.
Jonan AB, Kaye AD, Urman RD: Buprenorphine formulations: Clinical best practice strategies recommendations for perioperative management of patients undergoing surgical or interventional pain procedures. Pain Phys. 2018; 1(1): E1-E12.
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