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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 -
The Hastings Center Report Jan 2020I first became aware of bioethics in the spring of 1980. I had spent a thirty-six-hour shift shadowing a medical resident, and I was struck that many of the resident's...
I first became aware of bioethics in the spring of 1980. I had spent a thirty-six-hour shift shadowing a medical resident, and I was struck that many of the resident's decisions had ethical dimensions. The next day, I came across the Hastings Center Report, and I realized I wanted to explore ethical issues I found implicit in clinical care, even though I still wanted to become a pediatrician. In September 2019, when I attended my first meeting of the U.S. Food and Drug Administration's Pediatric Advisory Committee, as a pediatric pulmonologist, I had the same sense of awe and curiosity that I had forty years ago. What had appeared initially as somewhat technical decisions about the regulation of drug labeling was suffused with ethical questions. The committee was asked to discuss possible changes to the labeling of two previously approved drugs.
Topics: Acetates; Advisory Committees; Bioethics; Cyclopropanes; Drug Labeling; Humans; Oxymorphone; Pediatrics; Quinolines; Sulfides; United States; United States Food and Drug Administration
PubMed: 32068277
DOI: 10.1002/hast.1074 -
Journal of Clinical Pharmacology Aug 2013This study evaluated the plasma concentrations of oxycodone and its demethylates and opioid-induced adverse effects based on cachexia stage in cancer patients receiving... (Clinical Trial)
Clinical Trial
This study evaluated the plasma concentrations of oxycodone and its demethylates and opioid-induced adverse effects based on cachexia stage in cancer patients receiving oxycodone. Seventy patients receiving oxycodone for cancer pain were enrolled. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined at the titration dose. Opioid-induced adverse effects were monitored for 2 weeks after the titration. Plasma concentrations of oxycodone and oxymorphone but not noroxycodone in patients with a GPS of 2 were significantly higher than that with a GPS of 0. The metabolic ratios of noroxycodone but not oxymorphone to oxycodone in patients with a GPS of 1 and 2 were significantly lower than in those with a GPS of 0. A higher GPS was associated with a higher incidence of somnolence, while the GPS did not affect the incidence of vomiting. Plasma concentrations of oxycodone and oxymorphone were not associated with the incidence of adverse effects. In conclusion, cancer cachexia raised the plasma exposures of oxycodone and oxymorphone through the reduction of CYP3A but not CYP2D6. Although the cachexia elevated the incidence of somnolence, alterations in their pharmacokinetics were not associated with the incidence.
Topics: Aged; Analgesics, Opioid; Cachexia; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Female; Humans; Male; Middle Aged; Morphinans; Neoplasms; Oxycodone; Oxymorphone; Pain
PubMed: 23733622
DOI: 10.1002/jcph.112 -
Veterinary Anaesthesia and Analgesia Sep 2013To evaluate the pharmacokinetics, in dogs, of liposome-encapsulated oxymorphone and hydromorphone made by the ammonium sulfate gradient loading technique (ASG).
OBJECTIVE
To evaluate the pharmacokinetics, in dogs, of liposome-encapsulated oxymorphone and hydromorphone made by the ammonium sulfate gradient loading technique (ASG).
ANIMALS
Four healthy purpose-bred Beagles aged 9.5 ± 3.2 months and weighing 13.4 ± 2.3 kg.
STUDY DESIGN
Randomized cross-over design.
METHODS
Each dog was given either 4.0 mg kg(-1) of ASG-oxymorphone or 8.0 mg kg(-1) of ASG-hydromorphone SC on separate occasions with a 3-month washout period. Blood was collected at baseline and at serial time points up to 1032 hours (43 days) after injection for determination of serum opioid concentrations. Serum opioid concentrations were measured with HPLC-MS and pharmacokinetic parameters were calculated using commercial software and non-compartmental methods.
RESULTS
Serum concentrations of oxymorphone remained above the limit of quantification for 21 days, while those for hydromorphone remained above the limit of quantification for 29 days. Cmax for ASG-oxymorphone was 7.5 ng mL(-1) ; Cmax for ASG-hydromorphone was 5.7 ng mL(-1) .
CONCLUSIONS AND CLINICAL RELEVANCE
Oxymorphone and hydromorphone, when encapsulated into liposomes using the ammonium sulfate gradient loading technique, result in measureable serum concentrations for between 3 to 4 weeks. This formulation may have promise in the convenient use of opioids for clinical treatment of chronically painful conditions in dogs.
Topics: Ammonium Sulfate; Analgesics, Opioid; Animals; Area Under Curve; Dogs; Half-Life; Hydromorphone; Liposomes; Male; Oxymorphone
PubMed: 23601353
DOI: 10.1111/vaa.12042 -
Pain Management Nov 2017Characterize the pharmacokinetic profile and tolerability of two tocopheryl phosphate mixture/oxymorphone patch formulations in healthy subjects, and the active... (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
Characterize the pharmacokinetic profile and tolerability of two tocopheryl phosphate mixture/oxymorphone patch formulations in healthy subjects, and the active metabolite (6-OH-oxymorphone).
MATERIALS & METHODS
Fifteen participants received a single application of oxymorphone patches +/- capsaicin for 72 h and were crossed-over for another 72 h.
RESULTS
Plasma oxymorphone was detected approximately 7 h and 6-OH-oxymorphone after approximately 18-19 h postapplication of both formulations, respectively. For oxymorphone, median t was 24 h, and C/C ratio was approximately 2.4. The most frequently reported treatment-related adverse event was application site reaction, mainly with capsaicin formulation.
CONCLUSION
Tocopheryl phosphate mixture/oxymorphone transdermal patches can successfully deliver therapeutic amounts of oxymorphone in a sustained manner over 72 h and are well tolerated. ANZCTR registration number: ACTRN12614000613606.
Topics: Adult; Analgesics, Opioid; Capsaicin; Cross-Over Studies; Drug Combinations; Humans; Male; Oxymorphone; Pain Management; Transdermal Patch; Young Adult; alpha-Tocopherol
PubMed: 28814158
DOI: 10.2217/pmt-2017-0032 -
Journal of Pharmaceutical and... Sep 2021A range of opioids are commonly prescribed to manage chronic pain, but individual patient responses vary greatly, especially in older populations. One source of that...
Simultaneous LC-MS/MS quantification of oxycodone, tramadol and fentanyl and their metabolites (noroxycodone, oxymorphone, O- desmethyltramadol, N- desmethyltramadol, and norfentanyl) in human plasma and whole blood collected via venepuncture and volumetric absorptive micro sampling.
INTRODUCTION
A range of opioids are commonly prescribed to manage chronic pain, but individual patient responses vary greatly, especially in older populations. One source of that variability are differences in absorption, metabolism and excretion, i.e. pharmacokinetics. Blood, plasma and serum concentrations of opioids allow that variability to be quantified and may be used to optimise opioid dosing. As an aid to that process, there is an unmet need to rapidly quantify several opioids and their metabolites in a single analytical method.
AIMS
To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous quantification of tramadol, oxycodone, fentanyl and their major metabolites in various human matrices.
METHODS
Sample preparation involved adding three deuterated internal standards followed by protein precipitation with 100 % acetonitrile, evaporation and reconstitution. Separation of analytes via LC was achieved on a reversed phase column via binary gradient elution using 0.005 % formic acid in water and 100 % acetonitrile as mobile phases. Analytes were detected via MS/MS with multiple reaction monitoring (MRM).
RESULTS
The method was accurate with the inter-day and intra-day accuracy of quality control samples (QCs) below 15 %. It was also precise with inter-day and intra-day coefficient of variation below 15 %. The lower limit of quantification (LLOQ) was 0.2 ng/mL for all analytes except tramadol and its metabolites, where the LLOQ was 10 ng/mL. Recovery was greater than 88 % for all analytes, except for O-desmethyltramadol (81 %). Analytes were stable over four freeze-thaw cycles, for 24 h on the bench top and for 24 h post-preparation. The inter- and intra-day variability of concentrations determined in blood and plasma were within 84-124%, whereas the inter- and intra-day variability for blood samples prepared using volumetric absorptive micro-sampling (VAMS) compared to those prepared from whole blood ranged between 83-122%.
CONCLUSION
A LC-MS/MS method is described that is able to accurately and precisely quantify a number of commonly prescribed opioids and their major metabolites in plasma and whole blood, including whole blood collected using VAMS.
Topics: Aged; Chromatography, Liquid; Fentanyl; Humans; Morphinans; Oxycodone; Oxymorphone; Reproducibility of Results; Tandem Mass Spectrometry; Tramadol
PubMed: 34087551
DOI: 10.1016/j.jpba.2021.114171 -
Current Medical Research and Opinion Aug 2010To evaluate the influence of age, sex, and previous opioid experience on the likelihood of successfully titrating opioid-naive and experienced patients with chronic low...
OBJECTIVE
To evaluate the influence of age, sex, and previous opioid experience on the likelihood of successfully titrating opioid-naive and experienced patients with chronic low back pain (CLBP) to an effective and well-tolerated dose of oxymorphone extended release (ER).
METHODS
Post hoc analysis of open-label titration phases of two enriched-enrollment randomized-withdrawal phase III trials in 575 adults with moderate-to-severe CLBP. Opioid-naive patients (n = 325) initiated oxymorphone ER at 10 mg/day (5 mg q12 h). Opioid-experienced patients (n = 250) initiated at a dose equianalgesic to their previous opioid and were allowed doses of 5 mg oxymorphone immediate-release rescue medication every 4-6 h, as needed. Oxymorphone ER was gradually titrated to a dose that reduced pain to
CLINICAL TRIAL REGISTRATION
NCT00225797, NCT00226421.
MAIN OUTCOME MEASURES
Number of patients reaching stabilized oxymorphone ER dose, reasons for treatment discontinuation in patients not reaching stabilized dose.
RESULTS
Open-label titration was successful in 61% (348/575) of patients, and similar proportions of men (63%) and women (59%) and opioid-naive (63%) and experienced (57%) patients. Patients aged >or=65 years were less likely than patients aged <65 years to complete titration (45 vs. 63%; p = 0.002; 95% CI, -0.30 to -0.06) and more likely to discontinue owing to adverse events (40 vs. 15%; p < 0.001; 95% CI, 0.14-0.36). Oxycodone-experienced patients were less likely than hydrocodone-experienced patients to complete titration (46 vs. 62%, p = 0.03; 95% CI,-0.30 to -0.02). Among successfully titrated patients, pain decreased regardless of prior opioid therapy, sex, or age.
CONCLUSIONS
Most patients with CLBP were titrated to an effective, generally well-tolerated oxymorphone ER dose. Older patients and those converted from oxycodone may require more gradual titration. A study limitation is that patients initiated oxymorphone ER to comply with protocol, whereas treatment failure typically motivates opioid initiation or switching in clinical practice.
Topics: Aged; Analgesics, Opioid; Chronic Disease; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Humans; Hydromorphone; Low Back Pain; Male; Middle Aged; Oxycodone; Oxymorphone; Pain Measurement; Patient Acceptance of Health Care; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome; Treatment Outcome
PubMed: 20521870
DOI: 10.1185/03007995.2010.490457 -
Research in Veterinary Science 1998The effects of transdermal fentanyl and i.m. oxymorphone on behavioural and physiological responses, after ovariohysterectomy in dogs, were investigated. The study...
The effects of transdermal fentanyl and i.m. oxymorphone on behavioural and physiological responses, after ovariohysterectomy in dogs, were investigated. The study involved three groups of 10 dogs: fentanyl/surgery (FS), oxymorphone/surgery (OS), fentanyl/control (FC). A transdermal fentanyl delivery system (50 microg hour(-1)) (FS and FC) was applied 20 hours before surgery, or i.m. oxymorphone (OS) was administered. After ovariohysterectomy (FS and OS) or anaesthesia alone (FC), dogs were continuously videotaped for 24 hours and a standardised hourly interaction with a handler performed. The videotapes were analysed, and interactive and non-interactive behaviours evaluated. In addition, pain and sedation scores, pulse and respiratory rates, rectal temperature, arterial blood pressure, plasma cortisol and plasma fentanyl concentrations were measured. This study showed that transdermal fentanyl and i.m. oxymorphone (0.05 mg kg(-1)) produced comparable analgesic effects over a 24 hour recording period. I.m. oxymorphone produced significantly more sedation and lower rectal temperatures than transdermal fentanyl. There were no significant differences between groups in respiratory and heart rates, and arterial blood pressures.
Topics: Administration, Cutaneous; Analgesics, Opioid; Animals; Behavior, Animal; Dogs; Female; Fentanyl; Hysterectomy; Injections, Intramuscular; Ovariectomy; Oxymorphone; Postoperative Period
PubMed: 9915151
DOI: 10.1016/s0034-5288(98)90151-5 -
Veterinary Anaesthesia and Analgesia Jan 2006To quantify the change in the minimum alveolar concentration (MAC) of isoflurane (ISO) associated with oxymorphone (OXY) or hydromorphone (HYDRO) in dogs. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To quantify the change in the minimum alveolar concentration (MAC) of isoflurane (ISO) associated with oxymorphone (OXY) or hydromorphone (HYDRO) in dogs.
DESIGN
Randomized crossover study with at least 1 week between assessments.
ANIMALS
Six young, healthy, mixed-breed dogs (1-3 years old), weighing 24.7 +/- 4.70 kg.
METHODS
Following mask induction, anesthesia was maintained with ISO in 100% O(2) using mechanical ventilation. The dogs received 0.05 mg kg(-1) OXY, 0.1 mg kg(-1) HYDRO, or 1 mL saline (control) IV. Following equilibration (15 minutes) at each percentage ISO tested, a supramaximal electrical stimulus was applied to the toe web and the response was assessed. Two separate MAC determinations were carried out during 4.5 hours of anesthesia, with completion of the evaluations at 1.5-2 and 4-4.5 hours after drug administration. A two-factor anova was used to determine whether there was a time or treatment effect on MAC and a Tukey test compared the drug effects at each time. Significance is reported at p < 0.05.
RESULTS
The mean MAC values (+/-SD) were 1.2 +/- 0.18 and 1.2 +/- 0.16% for control, 0.7 +/-0.15 and 1.0 +/- 0.15% for OXY, and 0.6 +/- 0.14 and 0.8 +/- 0.17% for HYDRO. The initial MAC with OXY and the MAC determined at both times with HYDRO were significantly different from the control MAC values.
CONCLUSIONS
Both OXY and HYDRO significantly reduced the MAC of ISO in dogs at 2 hours. At approximately 4.5 hours, HYDRO had a significant MAC-sparing effect, whereas OXY did not.
CLINICAL RELEVANCE
Although both OXY and HYDRO resulted in a significant reduction in the MAC of ISO at approximately 2 hours, HYDRO may be preferred for procedures of long duration and rarely needs repeated dosing before 4.5 hours.
Topics: Adjuvants, Anesthesia; Anesthetics, Inhalation; Animals; Cross-Over Studies; Dogs; Female; Hydromorphone; Isoflurane; Male; Oxymorphone; Pulmonary Alveoli
PubMed: 16412134
DOI: 10.1111/j.1467-2995.2005.00215.x -
Journal of Pharmaceutical Sciences Dec 1990Oxymorphone is a candidate for transdermal delivery since it is a very potent analgesic, is not very effective orally, and has a short duration of action. In developing...
Oxymorphone is a candidate for transdermal delivery since it is a very potent analgesic, is not very effective orally, and has a short duration of action. In developing a transdermal delivery system, two criteria that were considered important were achieving adequate flux and minimizing the lag time. Oxymorphone skin permeation rates in vitro were very low unless skin permeation enhancers were included in the vehicle. After an initial screen of 17 formulations, two skin permeation-enhancing formulations were selected for further study. These were myristic acid:propylene glycol:oxymorphone base (A), and decylmethylsulfoxide:ethanol:water:oxymorphone.HCl (B). With either formulation and either human or hairless guinea pig skin, there was little dependence of either in vitro flux or lag time on the section of skin used (stratum corneum, epidermis, epidermis/dermis). There were significant differences between human skin and hairless guinea pig skin when comparing in vitro fluxes with the two formulations. With formulation A, fluxes through hairless guinea pig skin were three-to fivefold greater than through human skin. With B, however, fluxes through human skin were up to fivefold greater than through hairless guinea pig skin. In vitro lag times with A were generally long (approximately 24 h), whereas those with B were much lower (approximately 1 to 10 h). The species dependence of permeation enhancement and the differences in lag time between formulations could be related to differences in the mechanisms of permeation enhancement. In vivo lag times with the fatty acid:propylene glycol vehicle were estimated in hairless guinea pigs based on plasma oxymorphone concentrations. These were much lower than in vitro lag times.
Topics: Administration, Cutaneous; Adolescent; Adult; Aged; Animals; Chemistry, Pharmaceutical; Drug Design; Female; Guinea Pigs; Humans; Male; Middle Aged; Myristic Acid; Myristic Acids; Oxymorphone; Skin Absorption; Time Factors
PubMed: 2079653
DOI: 10.1002/jps.2600791207