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Psychopharmacology Sep 2021Intravenous (IV) misuse of the µ opioid analgesic oxymorphone has caused significant public health harms; however, no controlled data on its IV abuse potential are... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Intravenous (IV) misuse of the µ opioid analgesic oxymorphone has caused significant public health harms; however, no controlled data on its IV abuse potential are available. The primary aims of this pilot study were to directly compare IV oxymorphone to IV oxycodone, morphine, and hydromorphone on a subjective measure of drug liking and to assess relative potency.
METHODS
Participants (n = 6) with opioid use disorder, physical dependence, and current IV use completed this two-site, within-subject, double-blind, placebo-controlled, inpatient pilot study. During each session, one IV dose (mg/70 kg) was administered: oxymorphone (1.8, 3.2, 5.6, 10, 18, 32), hydromorphone (1.8, 3.2, 5.6, 10, 18), oxycodone (18, 32, 56), morphine (18, 32), and placebo. Data were collected before and for 6 h after dosing. Primary outcomes included safety/physiological effects, subjective reports of drug liking, and relative potency estimates.
RESULTS
All active test drugs produced prototypical, dose-related µ opioid agonist effects (e.g., miosis). Oxymorphone was more potent than the comparator opioids on several measures, including drug liking and respiratory depression (p < 0.05). Across abuse-related subjective outcomes, oxymorphone was 2.3-2.8-fold more potent than hydromorphone and 12.5-14-fold more potent than oxycodone (p < 0.05).
CONCLUSIONS
Despite the relatively small sample size, this pilot study detected robust oxymorphone effects. Oxymorphone was far more potent than the comparator opioids, particularly on abuse potential outcomes. Overall, these findings may help explain surveillance reports that demonstrate, after adjusting for prescription availability, oxymorphone is injected at the highest frequency, relative to other prescription opioids.
Topics: Analgesics, Opioid; Humans; Opioid-Related Disorders; Oxycodone; Oxymorphone; Pilot Projects
PubMed: 34106317
DOI: 10.1007/s00213-021-05872-1 -
Journal of Pharmaceutical and... Apr 2018Oxycodone is a widely prescribed, full agonist opioid analgesic. As such, it is used clinically to treat different kinds of painful conditions, with a relatively high...
Oxycodone is a widely prescribed, full agonist opioid analgesic. As such, it is used clinically to treat different kinds of painful conditions, with a relatively high potential for doping practices in athletes. In this paper, different classic and innovative miniaturised matrices from blood and urine have been studied and compared, to evaluate their relative merits and drawbacks within therapeutic drug monitoring (TDM) and to implement new protocols for anti-doping analysis. Plasma, dried blood spots (DBS) and dried plasma spots (DPS) have been studied for TDM purposes, while urine, dried urine spots (DUS) and volumetric absorptive microsamples (VAMS) from urine for anti-doping. These sampling techniques were coupled to an original bioanalytical method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the evaluation and monitoring of the levels of oxycodone and its major metabolites (noroxycodone and oxymorphone) in patients under pain management and in athletes. The method was validated according to international guidelines, with good results in terms of precision, extraction yield and accuracy for all considered micromatrices. Thus, the proposed sampling, pre-treatment and analysis are attractive strategies for oxycodone determination in human blood and urine, with advanced options for application to derived micromatrices. Microsampling procedures have significant advantages over classic biological matrices like simplified sampling, storage and processing, but also in terms of precision (<9.0% for DBS, <7.7% for DPS, <7.1% for DUS, <5.3% for VAMS) and accuracy (>73% for DBS, >78% for DPS, >74% for DUS, >78% for VAMS). As regards extraction yield, traditional and miniaturised sampling approaches are comparable (>67% for DBS, >74% for DPS, >75% for DUS, >75% for VAMS). All dried matrices have very low volumes, leading to a significant advantage in terms of analysis feasibility. On the other hand, this also leads to a corresponding decrease in the overall sensitivity.
Topics: Blood Specimen Collection; Body Fluids; Chromatography, Liquid; Doping in Sports; Dried Blood Spot Testing; Drug Monitoring; Humans; Miniaturization; Morphinans; Oxycodone; Oxymorphone; Plasma; Specimen Handling; Tandem Mass Spectrometry; Urine
PubMed: 29414014
DOI: 10.1016/j.jpba.2018.01.043 -
Journal of Analytical Toxicology May 2020A comparative analysis of enzyme-linked immunosorbent assay (ELISA) and quadrupole time-of-flight mass spectrometry (LC-QTOF) for the detection of opioids in blood...
A comparative analysis of enzyme-linked immunosorbent assay (ELISA) and quadrupole time-of-flight mass spectrometry (LC-QTOF) for the detection of opioids in blood samples is presented. The Orange County Crime Lab (OCCL) was concerned that the opioid drug class was not accurately detected at low concentrations due to the use of LC-QTOF as a non-targeted screening method for multiple classes of drugs. In order to investigate this issue, 968 ante-mortem and postmortem blood samples were analyzed by ELISA for the presence of the following opioids: morphine, morphine-glucuronide, codeine, codeine-glucuronide, hydrocodone, hydromorphone, hydromorphone-glucuronide, oxycodone, oxymorphone and oxymorphone-glucuronide. All samples had been previously analyzed by LC-QTOF. Overall, 84 samples tested positive for opioids. Discrepant samples between ELISA and LC-QTOF were analyzed by a liquid chromatography tandem mass spectrometry confirmation method in order to determine the true composition of the sample. Upon review of the discrepant samples, no forensically relevant concentration of opioids was missed by LC-QTOF. Thus, the ability of the OCCL's LC-QTOF screening method was verified to detect opioids at low concentrations.
Topics: Analgesics, Opioid; Chromatography, Liquid; Codeine; Enzyme-Linked Immunosorbent Assay; Humans; Hydrocodone; Hydromorphone; Morphine; Morphine Derivatives; Oxycodone; Oxymorphone; Substance Abuse Detection
PubMed: 31897469
DOI: 10.1093/jat/bkz109 -
Journal of Analytical Toxicology Dec 2020Opioids are the drugs most commonly detected in overdose deaths and the second most consumed worldwide. An analytical methodology has been optimized and fully validated...
Opioids are the drugs most commonly detected in overdose deaths and the second most consumed worldwide. An analytical methodology has been optimized and fully validated for the determination of codeine, morphine, 6-acetylmorphine, 6-acetylcodeine, oxycodone, oxymorphone and fentanyl in whole blood and pericardial fluid. The internal standards used were codeine-d3, morphine-d3, 6-acetylmorphine-d3 and fentanyl-d5. Before solid-phase extraction, volumes of 250 μL of blood and pericardial fluid were subjected to a protein precipitation (with 750 μL of ice-cold acetonitrile) and a microwave-induced oximation was performed using a solution of 1% aqueous hydroxylamine hydrochloride in phosphate-buffered saline (1:2, v/v). Finally, the dried extracts were further derivatized with a solution of n-methyl-n-(trimethylsilyl) trifluoroacetamide + 5% trimethylchlorosilane under microwave irradiation. The chromatographic analysis was carried out using gas chromatography-mass spectrometry operating in electron impact and selected ion monitoring mode. For all analytes, the method was linear between 5 and 1,000 ng/mL with determination coefficients (r2) >0.99. Depending on the analyte and matrix, the limit of detection varies between 3 and 4 ng/mL. Intra- and intermediate precision (<20%) and bias (±20%) were acceptable for all analytes in both matrices. The stability of the substances in the studied matrices was guaranteed, at least, 24 h in the autosampler, 4 h at room temperature and 30 days after three freeze/thaw cycles. This methodology was applied to real samples from the Laboratory of Chemistry and Forensic Toxicology, Centre Branch, of the National Institute of Legal Medicine and Forensic Sciences, Portugal.
Topics: Analgesics, Opioid; Drug Overdose; Fentanyl; Forensic Toxicology; Humans; Oxycodone; Pericardial Fluid; Substance Abuse Detection
PubMed: 32518955
DOI: 10.1093/jat/bkaa064 -
Annals of Translational Medicine Dec 2022Oxycodone is a commonly used oral opioid in children for treating postoperative pain. Highly polymorphic gene metabolizes oxycodone into its more potent metabolite,...
BACKGROUND
Oxycodone is a commonly used oral opioid in children for treating postoperative pain. Highly polymorphic gene metabolizes oxycodone into its more potent metabolite, oxymorphone. We hypothesized that altered activity due to polymorphisms will influence oxycodone requirements {relative oxycodone use [oxycodone morphine equivalents (MEq)/total MEq] to maintain analgesia} (primary outcome) and risk for oxycodone induced side-effects such as respiratory depression (RD) and emesis (secondary outcomes). We also explored the influence of genotype availability and provider guidance on oral opioid prescription patterns.
METHODS
Patients who underwent Nuss procedure and spine fusion with genotyping results available preoperatively were included. Data on demographics, genotypes, oral opioids, pain scores, RD and emesis were collected. Univariate and multivariable regression for comparison of genotype predicted poor, ultrarapid, intermediate metabolizers (PM, UM and IM) phenotype with normal metabolizers (NM) for outcomes were performed. Stratified logistic regression was conducted in low (oxycodone/total MEq <0.5) and high (and oxycodone/total MEq >0.5) oxycodone use groups for RD and emesis, with application of firth correction due to quasi-complete separations. Breslow-Day test was used to evaluate odds ratios for prescribing genotype directed opioid between control group (2012-15) (where providers were alerted to genotyping results availability but not directed to use them while prescribing) and genotype directed groups (2016-18) (where providers were directed to use the genotyping results available to them while prescribing oxycodone after surgery).
RESULTS
Of 193 subjects (age 15.9±0.25 years, 28.5% female, 93.78% White; 101 NM, 76 IM, 10 PM and 6 UM), 77.72% underwent pectus surgery. phenotype was associated with oxycodone MEq/total MEq requirements (P<0.001). Both PM and UM phenotypes had lower oxycodone requirements compared to NM [-0.316 (SE 0.098), P=0.005 and -0.432 (SE 0.113), P<0.001 respectively]. phenotype was associated with RD in high use oxycodone group (P=0.018) but not low use oxycodone groups (P=0.634). No phenotype association was found for emesis. Oxycodone was prescribed to 91.24% of NM/IM 66.67% of PM/UM (P=0.129) in control group and 94.64% of NM/IM 28.57% of PM/UM (P<0.001) in the genotype-directed group. PM/UM phenotypes in genotype directed group had a lower chance of being prescribed oxycodone (effect size =-2.775; SE 1.566; P=0.076).
CONCLUSIONS
Our findings suggest genotypes are associated with oxycodone requirements for analgesia and may influence risk for RD. Genotype availability and guidance likely influence oral opioid prescription pattern after surgery. Our findings are limited by small sample size for UM/PM groups.
PubMed: 36618804
DOI: 10.21037/atm-2022-58 -
Addiction Biology Jan 2016Oxymorphone is a semisynthetic μ-opioid agonist, marketed as a prescription analgesic purported to be twice as potent as oxycodone for pain relief. Oral formulations of... (Randomized Controlled Trial)
Randomized Controlled Trial
Oxymorphone is a semisynthetic μ-opioid agonist, marketed as a prescription analgesic purported to be twice as potent as oxycodone for pain relief. Oral formulations of oxymorphone were reintroduced in the United States in 2006 and reports of abuse ensued; however, there are limited data available on its pharmacodynamic effects. The current study aimed to examine the direct physiologic effects, relative abuse liability, analgesic profile and overall pharmacodynamic potency of oxymorphone in comparison with identical doses of oxycodone. Healthy, non-dependent opioid abusers (n = 9) were enrolled in this within-subject, double-blind, placebo-controlled, 3-week inpatient study. Seven experimental sessions (6.5 hours) were conducted, during which an oral dose of immediate-release formulations of oxymorphone (10, 20 and 40 mg), oxycodone (10, 20 and 40 mg) or placebo was administered. An array of physiologic, abuse liability and experimental pain measures was collected. At identical doses, oxymorphone produced approximately twofold less potent effects on miosis, compared with oxycodone. Oxymorphone also produced lesser magnitude effects on measures of respiratory depression, two experimental pain models and observer-rated agonist effects. However, 40 mg of oxymorphone was similar to 40 mg of oxycodone on several abuse-related subjective ratings. Formal relative potency analyses were largely invalid because of the substantially greater effects of oxycodone. Overall, oxymorphone is less potent on most pharmacodynamic measures, although at higher doses, its abuse liability is similar to oxycodone. These data suggest that the published clinical equianalgesic estimates may not be consistent with the observed direct physiologic effects of opioids, results of experimental pain models or abuse liability measures, as assessed in the human laboratory.
Topics: Administration, Oral; Adult; Analgesics, Opioid; Blood Pressure; Cognition; Cold Temperature; Cross-Over Studies; Double-Blind Method; Female; Heart Rate; Humans; Male; Opioid-Related Disorders; Oxymorphone; Pain; Pain Measurement; Pressure
PubMed: 25130052
DOI: 10.1111/adb.12173 -
American Journal of Preventive Medicine May 2018The U.S. is experiencing an opioid epidemic which is at least partially iatrogenic and fueled by both prescription and illicit misuse. This study provides a nationwide...
INTRODUCTION
The U.S. is experiencing an opioid epidemic which is at least partially iatrogenic and fueled by both prescription and illicit misuse. This study provides a nationwide examination of opioid distribution patterns during the last decade.
METHODS
Data were obtained from the U.S. Drug Enforcement Administration's Automation of Reports and Consolidated Orders System for 2006-2016. Analyses include quantities of ten opioids legally dispensed nationwide by weight and converted to Morphine Milligram Equivalents. Geospatial and state-level analyses were also completed in 2017.
RESULTS
The total for ten opioids peaked in 2011 (389.5 metric tons Morphine Milligram Equivalents) relative to both 2006 (286.1) and 2016 (364.6). Changes in the volume of opioids by weight over the decade were agent specific. Since 2011, there were decreases in hydrocodone (-28.4%); oxymorphone (-28.0%); fentanyl (-21.4%); morphine (-18.9%); oxycodone (-13.8%); and meperidine (-58.0%) and an increase in buprenorphine (75.2%) in 2016. There were substantial inter-state variations in rates with a fivefold difference between the highest Morphine Milligram Equivalents in 2016 (Rhode Island=2,623.7 mg/person) relative to the lowest (North Dakota=484.7 mg/person). An association was identified between state median age and per capita Morphine Milligram Equivalents (r =0.49, p<0.0005).
CONCLUSIONS
With the exception of buprenorphine, used to treat an opioid use disorder, prescription opioid use has been decreasing over the past 5 years in the U.S. Further efforts are needed to continue to optimize the balance between appropriate opioid access for acute pain while minimizing diversion and treating opioid addiction.
Topics: Analgesics, Opioid; Drug Prescriptions; Humans; Opioid-Related Disorders; Pain; Pharmacy Service, Hospital; Practice Patterns, Physicians'; Prescription Drug Misuse; Prescription Drugs; United States
PubMed: 29551331
DOI: 10.1016/j.amepre.2018.01.034 -
Pain Practice : the Official Journal of... Nov 2014A large percentage of patients with chronic pain on around-the-clock (ATC) opioids may experience increased pain occurring at the end of a scheduled dose, also known as... (Review)
Review
A large percentage of patients with chronic pain on around-the-clock (ATC) opioids may experience increased pain occurring at the end of a scheduled dose, also known as end-of-dose pain. Despite the significant prevalence and impact of end-of-dose pain in patients using extended-release (ER) opioids, there are no detailed analyses examining how the frequency of end-of-dose pain is linked to the formulations of long-acting opioids. Consequently, we performed a systematic review to evaluate how many published studies on patients with chronic cancer or noncancer pain identified end-of-dose pain. As only a few studies mentioned end-of-dose pain explicitly, we used breakthrough pain (BTP) as a surrogate parameter. We determined if any opioid formulation had a greater association with the frequency of BTP, the use of rescue medication for BTP, and the frequency of end-of-dose pain. Of the 39 studies entered in the final analysis, 14 studies across different formulations showed that ER opioids were effective in the prevention of BTP. The opioids most frequently studied were hydromorphone (26%), followed by morphine (23%), and transdermal buprenorphine (23%). Only 5% of the studies used immediate-release preparations. Overall, most studies showed that patients using ER preparations experienced fewer episodes of BTP compared with patients on placebo or an active comparator. This could reflect the favorable duration of action of these opioids compared with short-acting formulations. Future studies should examine the incidence of end-of-dose pain and use of rescue medicine in a longitudinal manner in patients with chronic pain taking short- vs. long-acting ATC opioids.
Topics: Analgesics, Opioid; Breakthrough Pain; Chronic Pain; Humans; Pain Measurement; Time; Treatment Outcome
PubMed: 24373184
DOI: 10.1111/papr.12156 -
Mayo Clinic Proceedings Jul 2020
Review
Topics: Administration, Intravenous; Analgesics, Opioid; Disease Outbreaks; Female; HIV Infections; Humans; Indiana; Male; Mass Screening; Narcotics; Needle-Exchange Programs; Oxymorphone; Substance Abuse, Intravenous
PubMed: 32622442
DOI: 10.1016/j.mayocp.2020.02.004 -
The Science of the Total Environment May 2019Opioids, both as prescription drugs and abuse substances, have been a hot topic and a focus of discussion in the media for the last few years. Although the literature...
Opioids, both as prescription drugs and abuse substances, have been a hot topic and a focus of discussion in the media for the last few years. Although the literature published shows the occurrence of opioids and some of their metabolites in the aquatic environment, there are scarce data in the application of high resolution mass spectrometry (HRMS) for the analysis of these compounds in the environment. The use of HRMS allows increasing the number of opioids that can be studied as well as the detection of unknown opioids, their metabolites and potential transformation products. In this work, a retrospective analysis for the identification of opioids and their metabolites using a curated database was applied to surface water and wastewater samples taken in the state of Minnesota (U.S.) in 2009, which were previously analyzed by liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS) for antidepressants. The database comprised >200 opioids including natural opiates (e.g. morphine and codeine), their semi-synthetic derivatives (e.g. heroin, hydromorphone, hydrocodone, oxycodone, oxymorphone, meperidine and buprenorphine), fully synthetic opioids (e.g. fentanyl, methadone, tramadol, dextromethorphan and propoxyphene), as well as some of their metabolites (e.g. 6-monoacetylcodeine, dextrorphan, EDDP, normorphine and O-desmethyltramadol). Moreover, additional MS-MS experiments were performed to confirm their identification, as well as to recognize fragmentation patterns and diagnostic ions for several opioids. These data provide a better understanding of the historical occurrence of opioids and their metabolites in surface waters impacted by wastewater sources. The concentrations of individual opioids in surface water and wastewater effluent varied from 8.8 (EDDP) to 1640 (tramadol) ngL and from 12 (dihydrocodeine) to 1288 (tramadol) ngL, respectively. The opioids with higher overall frequency detections were tramadol, dextromethorphan and its metabolite, dextrorphan.
Topics: Analgesics, Opioid; Chromatography, Liquid; Codeine; Data Analysis; Environmental Monitoring; Fentanyl; Heroin; Hydrocodone; Hydromorphone; Minnesota; Morphine; Morphine Derivatives; Oxycodone; Retrospective Studies; Substance Abuse Detection; Tandem Mass Spectrometry; Tramadol; Wastewater; Water Pollutants, Chemical
PubMed: 30769311
DOI: 10.1016/j.scitotenv.2019.01.389