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      Urine analysis of buprenorphine/norbuprenorphine/ naloxone in drugs and driving cases

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      Journal of Applied Bioanalysis

      Betasciencepress Publishing

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          Abstract

          Buprenorphine is now being detected as a drug of abuse in drugs/driving cases alongside side naloxone. Being a semi synthetic opiate, it has the potential to impair motorists in a similar fashion to morphine. Many laboratories have observed that buprenorphine does not produce a positive response with typical opiate immunoassays or routine basic GC-MS drug screens. In this study, samples of urine were enzymatically hydrolyzed after which they were extracted on mixed mode solid phase (SPE) columns, after which the extracted samples were analyzed by LC-MS/MS analysis in positive multiple reaction monitoring mode. The LOD/LOQ were determined to be 0.5 and 1.0 ng/mL, respectively for the analytes; linearity (10 to 1000 ng/mL) and (r2>0.999). The recovery of the analytes was found to be greater than 90%. Interday/intraday analysis was found to <8% and <10%, respectively. Matrix effects were determined to be <6%.

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          Current knowledge of buprenorphine and its unique pharmacological profile.

          Despite the increasing clinical use of transdermal buprenorphine, questions have persisted about the possibility of a ceiling effect for analgesia, its combination with other μ-opioid agonists, and the reversibility of side effects. In October 2008, a consensus group of experts met to review recent research into the pharmacology and clinical use of buprenorphine. The objective was to achieve consensus on the conclusions to be drawn from this work. It was agreed that buprenorphine clearly behaves as a full μ-opioid agonist for analgesia in clinical practice, with no ceiling effect, but that there is a ceiling effect for respiratory depression, reducing the likelihood of this potentially fatal adverse event. This is entirely consistent with receptor theory. In addition, the effects of buprenorphine can be completely reversed by naloxone. No problems are encountered when switching to and from buprenorphine and other opioids, or in combining them. Buprenorphine exhibits a pronounced antihyperalgesic effect that might indicate potential advantages in the treatment of neuropathic pain. Other beneficial properties are the compound's favorable safety profile, particularly in elderly patients and those with renal impairment, and its lack of effect on sex hormones and the immune system. The expert group agreed that these properties, as well as proven efficacy in severe pain and favorable tolerability, mean that buprenorphine can be considered a safe and effective option for treating chronic cancer and noncancer pain. © 2010 World Institute of Pain.
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            Pharmacokinetics and subjective effects of sublingual buprenorphine, alone or in combination with naloxone: lack of dose proportionality.

            Buprenorphine and buprenorphine/naloxone combinations are effective pharmacotherapies for opioid dependence, but doses are considerably greater than analgesic doses. Because dose-related buprenorphine opioid agonist effects may plateau at higher doses, we evaluated the pharmacokinetics and pharmacodynamics of expected therapeutic doses. The first experiment examined a range of sublingual buprenorphine solution doses with an ascending dose design (n = 12). The second experiment examined a range of doses of sublingual buprenorphine/naloxone tablets along with one dose of buprenorphine alone tablets with a balanced crossover design (n = 8). Twenty nondependent, opioid-experienced volunteers. Subjects in the solution experiment received sublingual buprenorphine solution in single ascending doses of 4, 8, 16 and 32 mg. Subjects in the tablet experiment received sublingual tablets combining buprenorphine 4, 8 and 16 mg with naloxone at a 4 : 1 ratio or buprenorphine 16 mg alone, given as single doses. Plasma buprenorphine, norbuprenorphine and naloxone concentrations and pharmacodynamic effects were measured for 48-72 hours after administration. Buprenorphine concentrations increased with dose, but not proportionally. Dose-adjusted areas under the concentration-time curve for buprenorphine 32 mg solution, buprenorphine 1 6 mg tablet and buprenorphine/naloxone 16/4 mg tablet were only 54 +/- 16%, 70 +/- 25% and 72 +/- 17%, respectively, of that of the 4 mg dose of sublingual solution or tablet. No differences were found between dose strengths for most subjective and physiological effects. Pupil constriction at 48 hours after administration of solution did, however, increase with dose. Subjects reported greater intoxication with the 32 mg solution dose, even though acceptability of the 4 mg dose was greatest. Naloxone did not change the bioavailability or effects of the buprenorphine 16 mg tablet. Less than dose-proportional increases in plasma buprenorphine concentrations may contribute to the observed plateau for most pharmacodynamic effects as the dose is increased.
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              Urinary Detection Times and Metabolite/Parent Compound Ratios After a Single Dose of Buprenorphine

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                Author and article information

                Journal
                Journal of Applied Bioanalysis
                J Appl Bioanal
                Betasciencepress Publishing
                2405710X
                July 15 2015
                July 15 2015
                : 1
                : 3
                : 80-88
                Article
                10.17145/jab.15.014
                © 2015

                This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/

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                Self URI (journal-page): https://jab.scholasticahq.com/

                General life sciences, Chemistry, Analytical chemistry, Life sciences

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