In-vitro and in-vivo characterization of a buprenorphine delivery system

Kleppner, Sofie R.; Patel, Raj; McDonough, Joseph M.; Costantini, Lauren C.

doi:10.1211/jpp.58.3.0002

Cited by 29 publications

(25 citation statements)

References 7 publications

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“…Buprenorphine release is dependent on the rate of dissolution and passive diffusion through the EVA copolymer matrix . Probuphine pharmacokinetics are consistent across all human clinical trials .…”

Section: General Informationmentioning

confidence: 83%

“…There was no evidence of nerve damage, implant migration or any attempted or unscheduled implant removal by patients. Histopathologically, in vivo responses to the implants appear biologically appropriate, and assuage with time …”

Section: Resultsmentioning

confidence: 99%

“…Despite key differences pharmacokinetically, the significance of a steady plasma concentration has not been prospectively studied. Upon explant, the rapid termination kinetics of Probuphine confirm the absence of unintended drug reservoirs in situ . This is desirable for patients requiring abrupt cessation due to adverse events.…”

Section: Discussionmentioning

confidence: 95%

“…Buprenorphine release is dependent on the rate of dissolution and passive diffusion through the EVA copolymer matrix. 15 Probuphine pharmacokinetics are consistent across all human clinical trials. 14,[16][17][18] Maximal plasma concentrations are achieved within 24 h of administration and decline exponentially to a low, non-fluctuating concentration from week 4 to week 24 eliminating typical peaks and troughs associated with SL administration.…”

Section: Pharmacokineticsmentioning

confidence: 96%

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Sustained‐release subdermal buprenorphine implants: the future of opioid use disorder management?

Shephard

Drovandi

2019

Pharmacy Practice and Res

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Aim To discuss the use of 6‐monthly buprenorphine implants for maintenance treatment of opioid use disorder and the potential clinical implications if approved in Australia. Data sources MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature and Web of Science were searched using the key terms ‘buprenorphine implant’, ‘opioid dependence’ and ‘Probuphine’ for articles published between January 2000 and August 2017. Study selection English‐language, peer‐reviewed articles were eligible for inclusion if they evaluated the effectiveness of buprenorphine implants for opioid dependence. Results After implantation, an initial pulse is followed by an exponential decline to a non‐fluctuating buprenorphine plasma concentration sustained over 6 months. In a double‐blind randomised controlled trial, buprenorphine implants were non‐inferior to low‐to‐moderate doses of sublingual buprenorphine (SLB) in clinically stable abstinent patients, with 6‐month abstinence being superior to SLB. Adverse effects are comparable to established buprenorphine preparations, although local issues from surgical implantation and explantation procedures appear commonplace, necessitating risk evaluation and mitigation strategies. No studies compared implantable buprenorphine to methadone, which retains patients in therapy more effectively than SLB at a fixed and low dose. Implants offer potential cost savings over SLB, with biannual dosing and tamper‐proof characteristics poised to address issues such as poor adherence, misuse, diversion and inadvertent exposures. Conclusion Buprenorphine implants have expanded the therapeutic repertoire for opioid use disorder, offering greater opportunity for treatment individualisation. Implants are currently indicated for a small subset of patients who have first demonstrated clinical stability on low‐to‐moderate doses of SLB. Preliminary data highlight their potential to hypothetically supersede existing treatment modalities in appropriately selected candidates.

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Section: General Informationmentioning

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 95%

Section: Pharmacokineticsmentioning

confidence: 96%

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Sustained‐release subdermal buprenorphine implants: the future of opioid use disorder management?

Shephard

Drovandi

2019

Pharmacy Practice and Res

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“…Polymer implants have been described for analgesia and addiction therapy. [1516] Yet, experience in our laboratory and others suggest drug release from polymers may be anomalous. [17] Moreover, polymer residues can induce an inflammatory response in tissues.…”

Section: Discussionmentioning

confidence: 99%

Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

et al. 2014

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Background:Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents.Objective:Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets.Methods:Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets.Results:Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant.Discussion:The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space.Conclusion:Drug implants can retain significant and unintended reservoirs of drugs.

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