Buprenorphine Research Articles

A qualitative study comparing physician-reported barriers to treating addiction using buprenorphine and extended-release naltrexone in U.S. office-based practices

AimOur aim was to compare physician-reported barriers to sublingual buprenorphine (BUP) and extended-release naltrexone (XR-NLT) prescribing in U.S. office-based practices, and to identify potential policies for minimizing these barriers. Only one previous qualitative study has examined physician-reported barriers to prescribing XR-NLT and no qualitative study has compared physician-reported barriers between the two medications. MethodsResearchers conducted individual semi-structured and in-depth interviews with 20 licensed physicians in four U.S. states between January 2016 and May 2017. Interview questions included general barriers to addiction treatment in office-based settings, barriers specific to BUP and XR-NLT prescribing, and potential government policies to decrease barriers. Researchers conducted thematic analysis of transcribed interviews. They developed and pilot tested a coding template based on a sample of transcripts, independently coded transcripts in Dedoose software, conducted consensus coding to eliminate coding discrepancies, and then assessed data for themes using research questions as a guide. ResultsGeneral barriers to office-based OUD treatment included limited physician education, limited insurance reimbursement, stigma, and perceptions of “difficult” patients. Barriers specific to BUP prescribing included regulatory restrictions, liability fears, and restrictions imposed by the criminal justice system. Barriers specific to XR-NLT prescribing included limited access to medically-supervised opioid detoxification, lack of awareness of the medication, and patient fears or disinterest. Participants without experience prescribing either medication emphasized barriers to treating OUD in general. Participants with experience prescribing BUP and/or XR-NLT described barriers to treating OUD in general as well as barriers specific to each medication. Policy makers should increase access to addiction medicine education, mandate insurance coverage of both medications and inpatient detoxification, prohibit excessive insurance prior authorization requirements, increase insurance reimbursement for behavioral healthcare, and incentivize interdisciplinary collaboration. ConclusionsWhile overlap exists, some barriers to BUP prescribing differ from barriers to XR-NLT prescribing.

620: Effect of opioid maintenance therapy on placental efficiency

Methadone (MET) and subutex (SUB) are used in medication assisted treatment (MAT) during pregnancy and cross the placenta. Infants exposed to MAT in utero are at risk for intrauterine growth restriction, but little is known about placental function. Placental efficiency (PE, birthweight in grams/ placental weight in grams) is lower in obstetrical complications affecting growth, including pre-eclampsia. We hypothesize that exposure to MAT is associated with lower placental efficiency. 64 patients treated with MET and 21 on SUB were included. A cohort of 565 women not exposed to opioids (non-MAT) was used as a comparison group. The association between placental efficiency and maternal characteristics was evaluated using a multiple linear regression model that included gestational age, maternal pre-pregnancy BMI, MAT program, race, and active cigarette smoking as covariates. One way ANOVA was performed in actively smoking Caucasian women at term, to assess differences between groups. In the regression model, PE was associated with gestational age, maternal pre-pregnancy BMI, Caucasian race, and maternal smoking. Thus, to assess PE differences between MAT groups, only term, Caucasians who smoked were analyzed. Placental weight (p=0.03) and birthweight (p=0.008) were significantly different between groups. MET treatment was associated with a larger placenta and smaller baby. Birthweight was also smaller in the SUB group. PE was decreased in the MET, but not SUB group as compared to non-MAT controls (p<0.005; Figure 1). MAT is associated with changes in placental efficiency, compared to women not exposed to MAT. Methadone treatment is associated with larger placentas, yet smaller babies, suggesting reduced placental function, confirmed by a lower placental efficiency. Alternatively, treatment with SUB lead to relatively efficient placentas, as compared to non-MAT controls. The association between MET treatment and decreased PE may support the preferred use of SUB in pregnancy.

Computational design, synthesis and utilization of a magnetic molecularly imprinted polymer on graphene oxide nanosheets for highly selective extraction and determination of buprenorphine in biological fluids and tablets

A magnetic MIP for the selective extraction of buprenorphine (BUP) from real plasma and urine samples and tablets based on computational design as a novel procedure has been developed.

Use of Metabolic Ratios of Drugs in Urine for Monitoring Pain Management Patients

This is my opinion about the utility of urine metabolic ratios (MRs)2 in the setting of providing laboratory services for pain management patients. In the following sections, I define the MR and some terms related to it, and describe the urine drug testing services at my institution. The MR's utility and limitations are then reviewed, followed by a summary. This institution's core/chemistry laboratory serves the immediate drug testing needs of the 950-bed main hospital, its emergency department, and an outpatient department generating about 1500 urine and 600 oral fluid drug screens per month; typically, fewer than 100 of the oral fluid screens have a simultaneously collected urine sample tested for comparison. Urine screens provide qualitative immunoassay results, and oral fluid tests provide quantitative LC-MS/MS results. Clarification of unexpected urine results is performed by LC-MS/MS at a reference laboratory after consultation between the ordering clinician and a laboratory director. The urine panel detects drugs prescribed for pain management as well as illicit drugs, and includes class-specific assays for benzodiazepines (BZ), buprenorphine (BUP), methadone (METHAD), opiates (OPI), and oxycodone (OXYCOD). The MR is the ratio of a drug metabolite concentration to its parent drug concentration, expressed as a range. A parent drug will have an MR for each of its main metabolites. …

EEOC files suit over Volvo's refusal to hire individual on buprenorphine

EEOC files suit over Volvo's refusal to hire individual on buprenorphine

Highly sensitive simultaneous quantification of buprenorphine and norbuprenorphine in human plasma by magnetic solid-phase extraction based on PpPDA/Fe3O4 nanocomposite and high-performance liquid chromatography

A rapid and sensitive method based on magnetic solid-phase extraction coupled to high-performance liquid chromatography with ultraviolet detection was developed for the simultaneous determination of buprenorphine (BPN) and its major metabolite, norbuprenorphine (N-BPN), in human plasma samples. Poly (para-phenylenediamine)-modified Fe3O4 nanoparticles (PpPDA/Fe3O4) were synthesized and used as a magnetic adsorbent for the extraction and preconcentration of BPN and N-BPN in biological samples. The synthesized nanocomposites were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, energy-dispersive X-ray spectroscopy and vibrating sample magnetometery. An isocratic separation was achieved on a Nova-Pak C18 reversed-phase column using a mobile phase consisting phosphate buffer (pH 3.4) and acetonitrile (50:50, v/v) at a flow rate of 1.0 mL min−1. The detection was conducted at 280 nm. Under the optimum conditions, the calibration curves for BPN and N-BPN were linear in the ranges 3.0–150.0 and 1.0–120.0 ng mL−1, respectively. The sensitivity was also high with limit of detection of 0.8 and 0.3 ng mL−1 for BPN and N-BPN in plasma, respectively. The method was successfully applied to the extraction and determination of BPN and N-BPN in human plasma samples with an average recovery of 98.10 and 96.41%, respectively.

Pregnancy Increases Norbuprenorphine Clearance in Mice by Induction of Hepatic Glucuronidation.

Norbuprenorphine (NBUP) is the major active metabolite of buprenorphine (BUP) that is commonly used to treat opiate addiction during pregnancy; it possesses 25% of BUP's analgesic activity and 10 times BUP's respiratory depression effect. To optimize BUP's dosing regimen during pregnancy with better efficacy and safety, it is important to understand how pregnancy affects NBUP disposition. In this study, we examined the pharmacokinetics of NBUP in pregnant and nonpregnant mice by administering the same amount of NBUP through retro-orbital injection. We demonstrated that the systemic clearance (CL) of NBUP in pregnant mice increased ∼2.5-fold compared with nonpregnant mice. Intrinsic CL of NBUP by glucuronidation in mouse liver microsomes from pregnant mice was ∼2 times greater than that from nonpregnant mice. Targeted liquid chromatography tandem-mass spectrometry proteomics quantification revealed that hepatic Ugt1a1 and Ugt2b1 protein levels in the same amount of total liver membrane proteins were significantly increased by ∼50% in pregnant mice versus nonpregnant mice. After scaling to the whole liver with consideration of the increase in liver protein content and liver weight, we found that the amounts of Ugt1a1, Ugt1a10, Ugt2b1, and Ugt2b35 protein in the whole liver of pregnant mice were significantly increased ∼2-fold compared with nonpregnant mice. These data suggest that the increased systemic CL of NBUP in pregnant mice is likely caused by an induction of hepatic Ugt expression and activity. The data provide a basis for further mechanistic analysis of pregnancy-induced changes in the disposition of NBUP and drugs that are predominately and extensively metabolized by Ugts.

Bupe and Vivitrol even in head‐to‐head study, if medication is taken

Bupe and Vivitrol even in head‐to‐head study, if medication is taken

Effectiveness of Injectable Extended-Release Naltrexone vs Daily Buprenorphine-Naloxone for Opioid Dependence

To date, extended-release naltrexone hydrochloride has not previously been compared directly with opioid medication treatment (OMT), currently the most commonly prescribed treatment for opioid dependence. To determine whether treatment with extended-release naltrexone will be as effective as daily buprenorphine hydrochloride with naloxone hydrochloride in maintaining abstinence from heroin and other illicit substances in newly detoxified individuals. A 12-week, multicenter, outpatient, open-label randomized clinical trial was conducted at 5 urban addiction clinics in Norway between November 1, 2012, and December 23, 2015; the last follow-up was performed on October 23, 2015. A total of 232 adult opioid-dependent (per DSM-IV criteria) individuals were recruited from outpatient addiction clinics and detoxification units and assessed for eligibility. Intention-to-treat analyses of efficacy end points were performed with all randomized participants. Randomization to either daily oral flexible dose buprenorphine-naloxone, 4 to 24 mg/d, or extended-release naltrexone hydrochloride, 380 mg, administered intramuscularly every fourth week for 12 weeks. Primary end points (protocol) were the randomized clinical trial completion rate, the proportion of opioid-negative urine drug tests, and number of days of use of heroin and other illicit opioids. Secondary end points included number of days of use of other illicit substances. Safety was assessed by adverse event reporting. Of 159 participants, mean (SD) age was 36 (8.6) years and 44 (27.7%) were women. Eighty individuals were randomized to extended-release naltrexone and 79 to buprenorphine-naloxone; 105 (66.0%) completed the trial. Retention in the extended-release naltrexone group was noninferior to the buprenorphine-naloxone group (difference, -0.1; with 95% CI, -0.2 to 0.1; P = .04), with mean (SD) time of 69.3 (25.9) and 63.7 (29.9) days, correspondingly (P = .33, log-rank test). Treatment with extended-release naltrexone showed noninferiority to buprenorphine-naloxone on group proportion of total number of opioid-negative urine drug tests (mean [SD], 0.9 [0.3] and 0.8 [0.4], respectively, difference, 0.1 with 95% CI, -0.04 to 0.2; P < .001) and use of heroin (mean difference, -3.2 with 95% CI, -4.9 to -1.5; P < .001) and other illicit opioids (mean difference, -2.7 with 95% CI, -4.6 to -0.9; P < .001). Superiority analysis showed significantly lower use of heroin and other illicit opioids in the extended-release naltrexone group. No significant differences were found between the treatment groups regarding most other illicit substance use. Extended-release naltrexone was as effective as buprenorphine-naloxone in maintaining short-term abstinence from heroin and other illicit substances and should be considered as a treatment option for opioid-dependent individuals. clinicaltrials.gov Identifier: NCT01717963.

Counseling with bupe: It doesn't hurt, but does it help?

Counseling with bupe: It doesn't hurt, but does it help?

Treatment of opioid dependence with buprenorphine: current update

Opioid maintenance treatment is the first-line approach in opioid dependence. Both the full opioid agonist methadone (MET) and the partial agonist buprenorphine (BUP) are licensed for the treatment of opioid dependence. BUP differs significantly from MET in its pharmacology, side effects, and safety issues. For example, the risk of respiratory depression is lower than with MET. The risk of diversion and injection of BUP have been reduced by also making it available as a tablet containing the opioid antagonist naloxone. This review summarizes the clinical effects of BUP and examines possible factors that can support decisions regarding the use of BUP or MET in opioid-dependent people.

A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration.

Opioid dependence is associated with high morbidity and mortality. Buprenorphine (BUP) is approved by the Food and Drug Administration to treat opioid dependence. There is a lack of clear consensus on the appropriate dosing of BUP due to interpatient physiological differences in absorption/disposition, subjective response assessment and other patient comorbidities. The objective of the present study was to build and validate robust physiologically based pharmacokinetic (PBPK) models for intravenous (IV) and sublingual (SL) BUP as a first step to optimizing BUP pharmacotherapy. BUP-PBPK modelling and simulations were performed using SimCyp® by incorporating the physiochemical properties of BUP, establishing intersystem extrapolation factors-based in vitro-in-vivo extrapolation (IVIVE) methods to extrapolate in vitro enzyme activity data, and using tissue-specific plasma partition coefficient estimations. Published data on IV and SL-BUP in opioid-dependent and non-opioid-dependent patients were used to build the models. Fourteen model-naïve BUP-PK datasets were used for inter- and intrastudy validations. The IV and SL-BUP-PBPK models developed were robust in predicting the multicompartment disposition of BUP over a dosing range of 0.3-32mg. Predicted plasma concentration-time profiles in virtual patients were consistent with reported data across five single-dose IV, five single-dose SL and four multiple dose SL studies. All PK parameter predictions were within 75-137% of the corresponding observed data. The model developed predicted the brain exposure of BUP to be about four times higher than that of BUP in plasma. The validated PBPK models will be used in future studies to predict BUP plasma and brain concentrations based on the varying demographic, physiological and pathological characteristics of patients.

Ryan Haight Act stands in way of buprenorphine telehealth

Ryan Haight Act stands in way of buprenorphine telehealth

Efficacy of Tramadol Extended-Release for Opioid Withdrawal

Opioid use disorder (OUD) is a significant public health problem. Supervised withdrawal (ie, detoxification) from opioids using clonidine or buprenorphine hydrochloride is a widely used treatment. To evaluate whether tramadol hydrochloride extended-release (ER), an approved analgesic with opioid and nonopioid mechanisms of action and low abuse potential, is effective for use in supervised withdrawal settings. A randomized clinical trial was conducted in a residential research setting with 103 participants with OUD. Participants' treatment was stabilized with morphine, 30 mg, administered subcutaneously 4 times daily. A 7-day taper using clonidine (n = 36), tramadol ER (n = 36), or buprenorphine (n = 31) was then instituted, and patients were crossed-over to double-blind placebo during a post-taper period. The study was conducted from October 25, 2010, to June 23, 2015. Retention, withdrawal symptom management, concomitant medication utilization, and naltrexone induction. Results were analyzed over time and using area under the curve for the intention-to-treat and completer groups. Of the 103 participants, 88 (85.4%) were men and 43 (41.7%) were white; mean (SD) age was 28.9 (10.4) years. Buprenorphine participants (28 [90.3%]) were significantly more likely to be retained at the end of the taper compared with clonidine participants (22 [61.1%]); tramadol ER retention was intermediate and did not differ significantly from that of the other groups (26 [72.2%]; χ2 = 8.5, P = .01). Time-course analyses of withdrawal revealed significant effects of phase (taper, post taper) for the Clinical Opiate Withdrawal Scale (COWS) score (taper mean, 5.19 [SE, .26]; post-taper mean, 3.97 [SE, .23]; F2,170 = 3.6, P = .03) and Subjective Opiate Withdrawal Scale (SOWS) score (taper mean,8.81 [SE, .40]; post-taper mean, 4.14 [SE, .30]; F2,170 = 15.7, P < .001), but no group effects or group × phase interactions. Analyses of area under the curve of SOWS total scores showed significant reductions (F2,159 = 17.7, P < .001) in withdrawal severity between the taper and post-taper periods for clonidine (taper mean, 13.1; post-taper mean, 3.2; P < .001) and tramadol ER (taper mean, 7.4; post-taper mean, 2.8; P = .03), but not buprenorphine (taper mean, 6.4; post-taper mean, 7.4). Use of concomitant medication increased significantly (F2,159 = 30.7, P < .001) from stabilization to taper in the clonidine (stabilization mean, 0.64 [SE, .05]; taper mean, 1.54 [SE, .10]; P < .001) and tramadol ER (stabilization mean, 0.53 [SE, .05]; taper mean, 1.19 [SE, .09]; P = .003) groups and from stabilization to post taper in the buprenorphine group (stabilization mean, 0.46 [SE, .05] post-taper mean, 1.17 [SE, .09]; P = .006), suggesting higher withdrawal for those groups during those periods. Naltrexone initiation was voluntary and the percentage of participants choosing naltrexone therapy within the clonidine (8 [22.2%]), tramadol ER (7 [19.4%]), or buprenorphine (3 [9.7%]) groups did not differ significantly (χ2 = 2.5, P = .29). The results of this trial suggest that tramadol ER is more effective than clonidine and comparable to buprenorphine in reducing opioid withdrawal symptoms during a residential tapering program. Data support further examination of tramadol ER as a method to manage opioid withdrawal symptoms. Clinicaltrials.gov Identifier: NCT01188421.

Combined treatment (Norspan, Gabapentin and Oxynorm) was found superior in pain management after total knee arthroplasty

Abstract Background Gabapentin (GAB) has recently been introduced for postoperative pain treatment in orthopedic surgery. As persistent postoperative pain is still a major problem in total knee arthroplasty (TKA), studies on the effect and side effects of Gabapentin in addition to the commonly used morphine (MOR), Oxynorm (OXY) and Norspan (NOR) are highly warranted. In the present study, four relevant treatment algorithms, gabapentin and morphine (GAB/MOR), gabapentin and Oxynorm (GAB/OXY), Oxynorm (OXY) and Gabapentin, Oxynorm and Norspan (GAB/OXY/NOR) were examined. Patients and methods A total of 241 patients were followed systematically during one month following TKA in four consecutive series: 60 patients were treated with GAB/MOR, 62 patients with GAB/OXY, 59 patients with OXY, and 60 patients with GAB/OXY/MOR. On the day before surgery and on postoperative day 1, 14, and 30, pain during rest, pain during walking and side effects (constipation, dizziness, and nausea) were reported (VAS). Results After 30 days, pain greatly decreased in all groups, with a superior effect of GAB/OXY/NOR for pain during rest and only slightly more side effects at day 1. Conclusions In management of postoperative pain following TKA, data indicated that GAB/OXY/NOR was superior, compared to GAB/MOR, GAB/OXY, and OXY.

Comparison of epidural Ropivacaine 0.75% and Ropivacaine 0.75% Plus Buprenorphine (0.5 ml) for total knee replacement surgery

Aim and Objectives: To assess the comparison between ropivacaine and combination of ropivacaine with buprenorphine in terms of onset and duration of analgesia, cardiorespiratory effects, side effects and post-operative analgesia. Methods: Total 60 adult patients of either sex, ASA grade I - II, schedule for total knee replacement surgery were enrolled in the study and randomized into two groups. Group R: received 14.5ml of 0.75% plain Ropivacaine + 0.5ml Normal saline (NS) making volume 15ml. Group RB: received 14.5ml of 0.75% plain Ropivacaine + Buprenorphine 150 mics (0.5ml) making volume 15ml. Onset of sensory-motor block, hemodynamic variables (HR, SBP, DPB, MAP, RR), duration of analgesia were recorded. Results: The onset of sensory blockade was earlier in group R as compared to in group RB. The motor onset time was similar in both the groups. The mean hemodynamic parameters were comparable in both the groups. Duration of analgesia was prolonged in group RB as compared to group R. Group RB had more incidences of post-op vomiting (36.67%) and pruritus (3.3%) as compared to group R. Conclusion: The addition of buprenorphine to epidural ropivacaine is a well tolerated, effective method for epidural anesthesia in patients undergoing unilateral total knee replacement surgery.

HHS secretary outrages field with methadone and buprenorphine remarks

HHS secretary outrages field with methadone and buprenorphine remarks

Report shows state‐by‐state variation in buprenorphine retention

Report shows state‐by‐state variation in buprenorphine retention

NPs and PAs ready to prescribe buprenorphine

NPs and PAs ready to prescribe buprenorphine

The Role of Norbuprenorphine in Buprenorphine‐Induced Neonatal Abstinence Syndrome: A Pilot Study

Opioid abuse during pregnancy may cause drug dependence in the fetus, and the abrupt discontinuation of opioid exposure at birth may induce neonatal abstinence syndrome (NAS) during the first week of life. NAS is characterized by inconsolable high‐pitched crying, tremor, vomiting, diarrhea, hypersensitivity, and sleep disturbances. Buprenorphine (BUP), a mu‐opioid receptor partial agonist, is administered as a substitution therapy to treat opioid use disorder during pregnancy. BUP improves neonatal outcome compared with methadone or no treatment, but BUP exposure often leads to NAS. Furthermore, NAS severity is independent of maternal BUP dose throughout pregnancy, suggesting that individual differences in maternal‐fetal BUP pharmacology may increase NAS susceptibility in some newborns. One possible explanation is that fetal exposure to norbuprenorphine (NorBUP), a metabolite of BUP that has high affinity and efficacy at the mu‐opioid receptor, differs across the BUP‐treated population and drives individual differences in the development of opioid dependence. This study tested the hypothesis that NorBUP can induce NAS. To test this hypothesis, we developed a novel model of NAS in which exposure to opioids occurs continuously across fetal development. Pregnant rats were implanted with subcutaneous minipumps containing NorBUP (0.1 or 0.3 mg/kg*day) or vehicle (5 % Emulphor) on gestation day (GD) 9. Treatment continued until delivery. Upon delivery, half of the pups were observed and scored for signs of precipitated withdrawal for 10 minutes after administration of the mu‐opioid receptor antagonist naltrexone (1 or 10 mg/kg, i.p.) or saline (10 ml/kg). Because of the CNS immaturity of the neonatal rat pup relative to the human newborn, this group models opioid dependence in preterm newborns. To model NAS at term, the other half of each litter was fostered to an untreated dam and received subcutaneous injections of NorBUP (0.05 mg/kg or 1.5 mg/kg) every 12 hours (BID) until they were tested for precipitated opioid withdrawal on postnatal day (PD) 7. Few withdrawal signs were observed in the pups tested within 24 hours of delivery, but PD7 pups exposed to the high dose of NorBUP in utero and after birth exhibited significantly more “wall climbing” and less “quiet” signs when challenged with naltrexone, indicating opioid withdrawal. The results of these preliminary studies suggest that NorBUP can induce opioid dependence in the neonatal pup. Ongoing experiments will determine fetal brain concentrations of NorBUP after maternal exposure to NorBUP (GD 9‐ GD20). Results of this experiment will be used to determine additional doses of NorBUP to be tested in the novel rat model of NAS.Support or Funding InformationSupport for this study was provided by the UAMS Fellow to Faculty award and the UAMS Tobacco Research Committee Tobacco Settlement Funds