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Blood Feb 2017
Topics: Analgesics, Opioid; Humans; Oxymorphone; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies
PubMed: 28209752
DOI: 10.1182/blood-2016-12-754507 -
Forensic Sciences Research 2017Wastewater-based epidemiology is an innovative approach that uses the analysis of human excretion products in wastewater to obtain information about exposure to drugs in...
Wastewater-based epidemiology is an innovative approach that uses the analysis of human excretion products in wastewater to obtain information about exposure to drugs in defined population groups. We developed and validated an analytical method for the simultaneous determination of opioids (morphine, oxycodone, hydrocodone, oxymorphone and hydromorphone), and cannabinoids (Δ-tetrahydrocannabinol, 11--9-carboxy-tetrahydrocannabinol (THCCOOH) and THCCOOH-glucuronide) in raw-influent wastewater samples by ultra-high performance liquid chromatography-tandem mass spectrometry. Method validation included linearity (5-1 000 ng/L for opioids, 10-1 000 ng/L for cannabinoids), imprecision (<21.2%), accuracy (83%-131%), matrix effect (from -35.1% to -14.7%) and extraction efficiency (25%-84%), limit of detection (1-5 ng/L) and quantification (5-10 ng/L) and auto-sampler stability (no loss detected). River and wastewater samples were collected in triplicate from different locations in New York City and stored at -20 °C until analysis. Water from sewage overflow location tested positive for morphine (10.7 ng/L), oxycodone (4.2-23.5 ng/L), oxymorphone (4.8 ng/L) and hydromorphone (4.2 ng/L). Raw influent wastewater samples tested positive for morphine (133.0-258.3 ng/L), oxycodone (31.1-63.6 ng/L), oxymorphone (16.0-56.8 ng/L), hydromorphone (6.8-18.0 ng/L), hydrocodone (4.0-12.8 ng/L) and THCCOOH (168.2-772.0 ng/L). This method is sensitive and specific for opioids and marijuana determination in wastewater samples.
PubMed: 30483615
DOI: 10.1080/20961790.2016.1270812 -
Clinical Chemistry and Laboratory... Aug 2017Oxycodone is a narcotic drug widely used to alleviate moderate and severe acute and chronic pain. Variability in analgesic efficacy could be explained by inter-subject...
Determination of oxycodone and its major metabolites noroxycodone and oxymorphone by ultra-high-performance liquid chromatography tandem mass spectrometry in plasma and urine: application to real cases.
BACKGROUND
Oxycodone is a narcotic drug widely used to alleviate moderate and severe acute and chronic pain. Variability in analgesic efficacy could be explained by inter-subject variations in plasma concentrations of parent drug and its active metabolite, oxymorphone. To evaluate patient compliance and to set up therapeutic drug monitoring (TDM), an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay was developed and validated for the parent drug and its major metabolites noroxycodone and oxymorphone.
METHODS
Extraction of analytes from plasma and urine samples was obtained by simple liquid-liquid extraction. The chromatographic separation was achieved with a reversed phase column using a linear gradient elution with two solvents: acetic acid 1% in water and methanol. The separated analytes were detected with a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI).
RESULTS
Separation of analytes was obtained in less than 5 min. Linear calibration curves for all the analytes under investigation in urine and plasma samples showed determination coefficients (r2) equal or higher than 0.990. Mean absolute analytical recoveries were always above 86%. Intra- and inter-assay precision (measured as coefficient of variation, CV%) and accuracy (measured as % error) values were always better than 13%. Limit of detection at 0.06 and 0.15 ng/mL and limit of quantification at 0.2 and 0.5 ng/mL for plasma and urine samples, respectively, were adequate for the purpose of the present study.
CONCLUSIONS
Rapid extraction, identification and quantification of oxycodone and its metabolites both in urine and plasma by UHPLC-MS/MS assay was tested for its feasibility in clinical samples and provided excellent results for rapid and effective drug testing in patients under oxycodone treatment.
Topics: Aged; Aged, 80 and over; Chromatography, High Pressure Liquid; Female; Humans; Male; Middle Aged; Morphinans; Oxycodone; Oxymorphone; Tandem Mass Spectrometry
PubMed: 28080998
DOI: 10.1515/cclm-2016-0990 -
Benzylideneoxymorphone: A new lead for development of bifunctional mu/delta opioid receptor ligands.Bioorganic & Medicinal Chemistry Letters Feb 2017Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR)...
Opioid analgesic tolerance remains a considerable drawback to chronic pain management. The finding that concomitant administration of delta opioid receptor (DOR) antagonists attenuates the development of tolerance to mu opioid receptor (MOR) agonists has led to interest in producing bifunctional MOR agonist/DOR antagonist ligands. Herein, we present 7-benzylideneoxymorphone (6, UMB 246) displaying MOR partial agonist/DOR antagonist activity, representing a new lead for designing bifunctional MOR/DOR ligands.
Topics: Analgesics; Animals; Benzylidene Compounds; Ligands; Mice; Oxymorphone; Pain; Receptors, Opioid, delta; Receptors, Opioid, mu
PubMed: 28011222
DOI: 10.1016/j.bmcl.2016.11.057 -
The American Journal of the Medical... Dec 2016Opiate pain reliever (OPR) misuse by injection is increasing in the United States. Infective endocarditis (IE), a devastating complication of injection OPR use, has been...
BACKGROUND
Opiate pain reliever (OPR) misuse by injection is increasing in the United States. Infective endocarditis (IE), a devastating complication of injection OPR use, has been understudied.
METHODS
We conducted a retrospective chart review of IE cases at an academic tertiary care hospital in North Carolina. Hospital admissions from 2009-2014 were screened for cases of definite IE. Subjects reporting injection drug use (IDU) were classified as IDU-IE, and compared to those without reported IDU, classified as No IDU-IE. Rates of IDU-IE and No IDU-IE, patient demographics, microbiologic data and outcomes were compared between the groups.
RESULTS
A total of 127 incident admissions for IE were identified, 48 (37.8%) were classified as IDU-IE and 79 (62.2%) as No IDU-IE. IDU-IE cases increased from 14% of hospitalizations for IE in 2009 to 56% in 2014; reporting of OPR injection increased in 2012 and continued through the study period. IDU-IE subjects were younger (32.6 ± 11.7 versus 54.4 ± 13.1, P < 0.0001), more likely to be single (n = 33 [68.8%] versus n = 23 [29.1%], P < 0.0001) and to reside in rural communities (n = 36 [75.0%] versus n = 25 [31.6%], P < 0.0001) than No IDU-IE subjects. Hospital length of stay (26 days versus 12 days, P < 0.0001) and intensive care unit length of stay (2 days versus 1 day, P = 0.04) were longer for IDU-IE patients and hospital mortality did not differ (10.4% IDU-IE versus 8.9% No IDU-IE, P = 0.77).
CONCLUSIONS
IDU-IE rates increased over time, and OPR injection use in rural communities appears to be a major contributor. Interventions to reduce IDU-IE and OPR misuse are needed to halt this growing epidemic in at-risk rural communities.
Topics: Adult; Aged; Analgesics, Opioid; Drug Users; Endocarditis; Female; Humans; Injections; Male; Middle Aged; Retrospective Studies; Southeastern United States; Young Adult
PubMed: 27916215
DOI: 10.1016/j.amjms.2016.08.010 -
Blood Feb 2017Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following IV abuse of extended-release oxymorphone hydrochloride...
Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following IV abuse of extended-release oxymorphone hydrochloride (Opana ER), an oral opioid for long-term treatment of chronic pain. Here, we present unique clinical features of 3 patients and investigate IV exposure to the tablet's inert ingredients as a possible causal mechanism. Guinea pigs were used as an animal model to understand the hematopathologic and nephrotoxic potential of the inert ingredient mixture (termed here as PEO+) which primarily contains high-molecular-weight polyethylene oxide (HMW PEO). Microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury were found in a group of 3 patients following recent injection of adulterated extended-release oxymorphone tablets. Varying degrees of cardiac involvement and retinal ischemia occurred, with TMA evident on kidney biopsy. A TMA-like state also developed in guinea pigs IV administered PEO+. Acute tubular and glomerular renal injury was accompanied by nonheme iron deposition and hypoxia-inducible factor-1α upregulation in the renal cortex. Similar outcomes were observed following dosing with HMW PEO alone. IV exposure to the inert ingredients in reformulated extended-release oxymorphone can elicit TMA. Although prescription opioid abuse shows geographic variation, all physicians should be highly inquisitive of IV drug abuse when presented with cases of TMA.
Topics: Acute Kidney Injury; Analgesics, Opioid; Animals; Delayed-Action Preparations; Female; Guinea Pigs; Humans; Kidney; Male; Oxymorphone; Polyethylene Glycols; Thrombotic Microangiopathies
PubMed: 27864296
DOI: 10.1182/blood-2016-08-736579 -
British Journal of Clinical Pharmacology Apr 2017This study aimed to characterize the pharmacokinetics of oxycodone and its major metabolites in infants and covered the age range between extremely preterm neonates and... (Clinical Trial)
Clinical Trial
AIMS
This study aimed to characterize the pharmacokinetics of oxycodone and its major metabolites in infants and covered the age range between extremely preterm neonates and 2-year-old infants.
METHODS
Seventy-nine infants (gestational age 23-42 weeks; postnatal age 0-650 days) received intravenous oxycodone hydrochloride trihydrate at a dose of 0.1 mg kg during or after surgery. Three to seven blood samples were taken from each infant, and plasma concentrations of oxycodone, noroxycodone, oxymorphone, and noroxymorphone were quantified. The unconjugated forms of these compounds were determined in urine collected after up to 24 or 48 h from 25 infants. Pharmacokinetics was determined using noncompartmental analysis and reported for six clinically relevant age groups based on postmenstrual age.
RESULTS
Oxycodone pharmacokinetics changed markedly with patient age. Preterm neonates were found to have the highest pharmacokinetic variability out of the study population. In extremely preterm neonates (n = 6) median of elimination half-life was 8.8 h (range 6.8-12.5), in preterm (n = 11) 7.4 h (4.2-11.6), and in older neonates (n = 22) 4.1 h (2.4-5.8), all of which were significantly longer than that in infants aged 6-24 months (n = 12) 2.0 h (1.7-2.6). Median renal clearance was fairly constant in all age groups, whereas non-renal clearance markedly increased with age. Noroxycodone was the major metabolite in plasma and urine.
CONCLUSIONS
Oxycodone elimination is slower and pharmacokinetic variability more pronounced in neonates when compared to older infants. These findings highlight the importance of careful dose titration for neonates.
Topics: Age Factors; Analgesics, Opioid; Child, Preschool; Female; Half-Life; Humans; Infant; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Male; Morphinans; Oxycodone; Prospective Studies; Time Factors
PubMed: 27780305
DOI: 10.1111/bcp.13164 -
Journal of the American Geriatrics... Sep 2016To estimate the prevalence of new initiation of long-acting opioids since introduction of national efforts to increase prescriber and public awareness on safe use of... (Comparative Study)
Comparative Study
OBJECTIVES
To estimate the prevalence of new initiation of long-acting opioids since introduction of national efforts to increase prescriber and public awareness on safe use of transdermal fentanyl patches.
DESIGN
Cross-sectional.
SETTING
U.S. nursing homes (NHs).
PARTICIPANTS
Medicare-enrolled long-stay NH residents (N = 22,253).
MEASUREMENTS
Minimum Data Set 3.0 was linked with Medicare enrollment, hospital claims, and prescription drug transaction data (January-December 2011) and used to determine the prevalence of new initiation of a long-acting opioid prescribed to residents in NHs.
RESULTS
Of NH residents prescribed a long-acting opioid within 30 days of NH admission (n = 12,278), 9.4% (95% confidence interval = 8.9-9.9%) lacked a prescription drug claim for a short-acting opioid in the previous 60 days. The most common initial prescriptions of long-acting opioids were fentanyl patch (51.9% of opioid-naïve NH residents), morphine sulfate (28.1%), and oxycodone (17.2%).
CONCLUSION
New initiation of long-acting opioids-especially fentanyl patches, which have been the subject of safety communications-persists in NHs.
Topics: Administration, Cutaneous; Aged; Aged, 80 and over; Analgesics, Opioid; Buprenorphine; Chronic Pain; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Utilization; Female; Fentanyl; Homes for the Aged; Humans; Long-Term Care; Male; Morphine; Nursing Homes; Oxycodone; Oxymorphone; Practice Patterns, Physicians'; Rhode Island; Tramadol
PubMed: 27487158
DOI: 10.1111/jgs.14306 -
Clinical Kidney Journal Aug 2016Thrombotic microangiopathy (TMA) associated with injecting sustained-release oxymorphone, an opioid intended for oral use, has previously been reported. We report a case...
Thrombotic microangiopathy (TMA) associated with injecting sustained-release oxymorphone, an opioid intended for oral use, has previously been reported. We report a case of TMA secondary to intravenous use of sustained-release oxycodone, and the first case to demonstrate relapsing disease due to persistent intravenous opioid use. In cases such as these, TMA is suspected to be due to a polyethylene oxide (PEO) coating found on these drugs, and the disease is likely due to a directly toxic effect of PEO to endothelial cells. We hypothesize that there are unidentified genetic predispositions causing some persons to be susceptible to developing this disease.
PubMed: 27478601
DOI: 10.1093/ckj/sfw039 -
The New England Journal of Medicine Jul 2016In January 2015, a total of 11 new diagnoses of human immunodeficiency virus (HIV) infection were reported in a small community in Indiana. We investigated the extent...
BACKGROUND
In January 2015, a total of 11 new diagnoses of human immunodeficiency virus (HIV) infection were reported in a small community in Indiana. We investigated the extent and cause of the outbreak and implemented control measures.
METHODS
We identified an outbreak-related case as laboratory-confirmed HIV infection newly diagnosed after October 1, 2014, in a person who either resided in Scott County, Indiana, or was named by another case patient as a syringe-sharing or sexual partner. HIV polymerase (pol) sequences from case patients were phylogenetically analyzed, and potential risk factors associated with HIV infection were ascertained.
RESULTS
From November 18, 2014, to November 1, 2015, HIV infection was diagnosed in 181 case patients. Most of these patients (87.8%) reported having injected the extended-release formulation of the prescription opioid oxymorphone, and 92.3% were coinfected with hepatitis C virus. Among 159 case patients who had an HIV type 1 pol gene sequence, 157 (98.7%) had sequences that were highly related, as determined by phylogenetic analyses. Contact tracing investigations led to the identification of 536 persons who were named as contacts of case patients; 468 of these contacts (87.3%) were located, assessed for risk, tested for HIV, and, if infected, linked to care. The number of times a contact was named as a syringe-sharing partner by a case patient was significantly associated with the risk of HIV infection (adjusted risk ratio for each time named, 1.9; P<0.001). In response to this outbreak, a public health emergency was declared on March 26, 2015, and a syringe-service program in Indiana was established for the first time.
CONCLUSIONS
Injection-drug use of extended-release oxymorphone within a network of persons who inject drugs in Indiana led to the introduction and rapid transmission of HIV. (Funded by the state government of Indiana and others.).
Topics: Adolescent; Adult; Coinfection; Contact Tracing; Disease Outbreaks; HIV Infections; HIV-1; Hepatitis C; Humans; Indiana; Male; Middle Aged; Needle Sharing; Oxymorphone; Phylogeny; Social Support; Substance Abuse, Intravenous; Young Adult
PubMed: 27468059
DOI: 10.1056/NEJMoa1515195