-
Journal of Palliative Care Jul 2021In efforts to reduce misuse of opioids, new abuse deterrent formulations of medications have been developed. Insurers increasingly give abuse-deterrent opioid...
BACKGROUND
In efforts to reduce misuse of opioids, new abuse deterrent formulations of medications have been developed. Insurers increasingly give abuse-deterrent opioid formulations preferred formulary status, which can result in required formulation rotation for patients. Xtampza® (oxycodone myristate extended-release) is an abuse-deterrent opioid formulation that maintains its extended-release properties with any physical manipulation. Blood levels of oxycodone myristate extended-release (OxyM-ER) may vary with dietary caloric and fat intake.
CASE DESCRIPTION
A woman with metastatic breast carcinoma had severe myalgias and arthralgias well-managed with oxycodone hydrochloride extended-release (OxyHCl-ER) and hydrocodone/acetaminophen. A switch from OxyHCl-ER to OxyM-ER resulted in worsened pain management, decreased functional status, and a referral to palliative care (PC). Recognizing calorie-depending pharmacokinetic variability with OxyM-ER, the interdisciplinary PC team obtained a detailed dietary history from the patient, which revealed a low-fat, low-calorie healthy diet with inconsistent meals. After repeated education, the patient changed her diet and had improved pain and functional status without increasing her total daily opioid dose.
CONCLUSION
The efficacy of OxyM-ER may be compromised in patients with cancer experiencing anorexia, decreased or inconsistent food intake, or low-fat/low-calorie diets. An interdisciplinary team approach can improve pain control in the setting of "forced" formulary switches to OxyM-ER.
Topics: Analgesics, Opioid; Biological Availability; Delayed-Action Preparations; Female; Humans; Myristates; Opioid-Related Disorders; Oxycodone
PubMed: 33327849
DOI: 10.1177/0825859720981330 -
ENeuro 2021The rat oxycodone and cocaine biobanks contain samples that vary by genotypes (by using genetically diverse genotyped HS rats), phenotypes (by measuring addiction-like... (Review)
Review
The rat oxycodone and cocaine biobanks contain samples that vary by genotypes (by using genetically diverse genotyped HS rats), phenotypes (by measuring addiction-like behaviors in an advanced SA model), timepoints (samples are collected longitudinally before, during, and after SA, and terminally at three different timepoints in the addiction cycle: intoxication, withdrawal, and abstinence or without exposure to drugs through age-matched naive rats), samples collected (organs, cells, biofluids, feces), preservation (paraformaldehyde-fixed, snap-frozen, or cryopreserved) and application (proteomics, transcriptomics, microbiomics, metabolomics, epigenetics, anatomy, circuitry analysis, biomarker discovery, etc.Substance use disorders (SUDs) are pervasive in our society and have substantial personal and socioeconomical costs. A critical hurdle in identifying biomarkers and novel targets for medication development is the lack of resources for obtaining biological samples with a detailed behavioral characterization of SUD. Moreover, it is nearly impossible to find longitudinal samples. As part of two ongoing large-scale behavioral genetic studies in heterogeneous stock (HS) rats, we have created two preclinical biobanks using well-validated long access (LgA) models of intravenous cocaine and oxycodone self-administration (SA) and comprehensive characterization of addiction-related behaviors. The genetic diversity in HS rats mimics diversity in the human population and includes individuals that are vulnerable or resilient to compulsive-like responding for cocaine or oxycodone. Longitudinal samples are collected throughout the experiment, before exposure to the drug, during intoxication, acute withdrawal, and protracted abstinence, and include naive, age-matched controls. Samples include, but are not limited to, blood plasma, feces and urine, whole brains, brain slices and punches, kidney, liver, spleen, ovary, testis, and adrenal glands. Three preservation methods (fixed in formaldehyde, snap-frozen, or cryopreserved) are used to facilitate diverse downstream applications such as proteomics, metabolomics, transcriptomics, epigenomics, microbiomics, neuroanatomy, biomarker discovery, and other cellular and molecular approaches. To date, >20,000 samples have been collected from over 1000 unique animals and made available free of charge to non-profit institutions through https://www.cocainebiobank.org/ and https://www.oxycodonebiobank.org/.
Topics: Animals; Behavior, Addictive; Biological Specimen Banks; Cocaine; Cocaine-Related Disorders; Oxycodone; Rats; Rats, Sprague-Dawley; Self Administration
PubMed: 33875455
DOI: 10.1523/ENEURO.0033-21.2021 -
Molecules (Basel, Switzerland) Sep 2019The total synthesis of (+)-10-keto-oxycodone was attained from phenethyl acetate in a stereoselective manner. Absolute stereochemistry was established via enzymatic...
The total synthesis of (+)-10-keto-oxycodone was attained from phenethyl acetate in a stereoselective manner. Absolute stereochemistry was established via enzymatic dihydroxylation of phenethyl acetate with the recombinant strain JM109 (pDTG601A) that furnished the corresponding -cyclohexadienediol whose configuration corresponds to the absolute stereochemistry of the ring C of (+)-10-keto-oxycodone. Intramolecular Heck reaction was utilized to establish the quaternary carbon at C-13, along with the dibenzodihydrofuran functionality. The C-14 hydroxyl and C-10 ketone were installed via SmI-mediated radical cyclization, and oxidation of a benzylic alcohol (obtained from an intermediate nitrate azide), respectively. The synthesis of (+)-10-keto-oxycodone was completed in a total of 14 operations (21 steps) and an overall yield of ~2%. Experimental and spectral data are provided for key intermediates and new compounds.
Topics: Acetates; Catalysis; Chemistry Techniques, Synthetic; Molecular Structure; Oxycodone; Stereoisomerism
PubMed: 31557873
DOI: 10.3390/molecules24193477 -
Advances in Therapy May 2011Two randomized, double-blind, placebo-controlled studies in acute and chronic pain treatment, powered to assess noninferiority of the efficacy of tapentadol immediate... (Comparative Study)
Comparative Study Randomized Controlled Trial
INTRODUCTION
Two randomized, double-blind, placebo-controlled studies in acute and chronic pain treatment, powered to assess noninferiority of the efficacy of tapentadol immediate release (IR) (50 mg, 75 mg) versus oxycodone hydrochloride (HCl) IR (10 mg), established comparable efficacy of tapentadol IR with oxycodone HCl IR, and suggested tapentadol IR's improved gastrointestinal tolerability. The impact of these equianalgesic doses of tapentadol and oxycodone HCl on bowel function and gastrointestinal tolerability was then directly assessed in the current study, using a validated bowel function diary to comprehensively assess opioid-induced constipation symptoms and outcomes.
METHODS
In this double-blind study, patients with end-stage joint disease were randomized to tapentadol IR (50 mg or 75 mg), oxycodone HCl IR 10 mg, or placebo. Treatment with IR formulations (14 days) was followed by treatment (28 days) with extended-release (ER) formulations of active drugs (or placebo).
RESULTS
Oxycodone HCl IR treatment significantly decreased (P<0.001) mean (SD) number of spontaneous bowel movements over the 14-day period (average per week: [6.7 (5.44)] versus tapentadol IR 50 mg [9.0 (4.04)], tapentadol IR 75 mg [8.6 (4.65)], and placebo [9.9 (5.16)]) (primary measure), confirming the tolerability findings of the earlier studies. Additionally, incidences of nausea and vomiting were significantly lower over the 14-day period (nominal P<0.001) for tapentadol IR 50 and 75 mg, versus oxycodone HCl IR 10 mg. Results with ER formulations of tapentadol and oxycodone HCl over a longer treatment period were consistent with those of IR formulations.
CONCLUSION
Tapentadol IR (50 mg, 75 mg) consistently demonstrated superior gastrointestinal tolerability, including for the most commonly reported events, such as nausea, vomiting, and constipation at doses that provide comparable efficacy with oxycodone HCl IR 10 mg. These findings validate and extend the tolerability findings of the two earlier studies that established comparable efficacy of these tapentadol and oxycodone HCl doses.
Topics: Aged; Analgesics, Opioid; Chronic Disease; Constipation; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Joint Diseases; Male; Middle Aged; Nausea; Oxycodone; Pain; Phenols; Tapentadol; Vomiting
PubMed: 21494892
DOI: 10.1007/s12325-011-0018-0 -
Chemical Research in Toxicology Jan 2021Cytochrome P450 3A4 is a highly polymorphic enzyme and metabolizes approximately 40%-60% of therapeutic drugs. Its genetic polymorphism may significantly affect the...
Cytochrome P450 3A4 is a highly polymorphic enzyme and metabolizes approximately 40%-60% of therapeutic drugs. Its genetic polymorphism may significantly affect the expression and function of CYP3A4 resulting in alterations of the pharmacokinetics and pharmacodynamics of the CYP3A4-mediated drugs. The purpose of this study was to evaluate the catalytic activities of 30 CYP3A4 nonsynonymous variants and wild type toward oxycodone in vitro. CYP3A4 proteins were incubated with oxycodone for 30 min at 37 °C and the reaction was terminated by cooling to -80 °C immediately. Ultraperformance liquid chromatography tandem mass-spectrometry was used to analyze noroxycodone, and kinetic parameters Km, Vmax, and intrinsic clearance (Vmax/Km) of noroxycodone were also determined. Compared with CYP3A4.1, 24 CYP3A4 variants (CYP3A4.2-.5, -.7-.16, -.18 and -.19, -.23 and -.24, -.28 and -.29, and -.31-.34) exhibited significantly decreased relative clearance values (from 4.82% ± 0.31% to 80.98% ± 5.08%), whereas CYP3A4.6, -.17, -.20, -.21, -.26, and -.30 displayed no detectable enzyme activity. As the first study of these alleles for oxycodone metabolism in vitro, results of this study may provide insight into establishing the genotype-phenotype relationship for oxycodone and serve as a reference for clinical administrators and advance the provision of personalized precision medicine.
Topics: Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Genetic Variation; Humans; Molecular Conformation; Oxycodone; Recombinant Proteins; Tandem Mass Spectrometry
PubMed: 33393779
DOI: 10.1021/acs.chemrestox.0c00361 -
Frontiers in Neural Circuits 2022Opioids are the most common medications for moderate to severe pain. Unfortunately, they also have addictive properties that have precipitated opioid misuse and the...
Opioids are the most common medications for moderate to severe pain. Unfortunately, they also have addictive properties that have precipitated opioid misuse and the opioid epidemic. In the present study, we examined the effects of acute administration of oxycodone, a μ-opioid receptor (MOR) agonist, on Ca transient activity of medium-sized spiny neurons (MSNs) in freely moving animals. Ca imaging of MSNs in dopamine D1-Cre mice (expressing Cre predominantly in the direct pathway) or adenosine A2A-Cre mice (expressing Cre predominantly in the indirect pathway) was obtained with the aid of miniaturized microscopes (Miniscopes) and a genetically encoded Cre-dependent Ca indicator (GCaMP6f). Systemic injections of oxycodone (3 mg/kg) increased locomotor activity yet, paradoxically, reduced concomitantly the number of active MSNs. The frequency of Ca transients was significantly reduced in MSNs from A2A-Cre mice but not in those from D1-Cre mice. For comparative purposes, a separate group of mice was injected with a non-Cre dependent Ca indicator in the cerebral cortex and the effects of the opioid also were tested. In contrast to MSNs, the frequency of Ca transients in cortical pyramidal neurons was significantly increased by oxycodone administration. Additional electrophysiological studies in brain slices confirmed generalized inhibitory effects of oxycodone on MSNs, including membrane hyperpolarization, reduced excitability, and decreased frequency of spontaneous excitatory and inhibitory postsynaptic currents. These results demonstrate a dissociation between locomotion and striatal MSN activity after acute administration of oxycodone.
Topics: Mice; Animals; Calcium; Oxycodone; Corpus Striatum; Neurons; Dopamine
PubMed: 36389179
DOI: 10.3389/fncir.2022.983323 -
Drugs 2005Oxycodone/ibuprofen 5 mg/400 mg (Combunox) is an oral fixed-dose combination tablet with analgesic, anti-inflammatory and antipyretic properties. It is approved in the... (Review)
Review
Oxycodone/ibuprofen 5 mg/400 mg (Combunox) is an oral fixed-dose combination tablet with analgesic, anti-inflammatory and antipyretic properties. It is approved in the US for the short-term (up to 7 days) management of acute, moderate-to-severe pain and is the first and only fixed-dose combination containing ibuprofen and oxycodone. A single dose of oxycodone/ibuprofen 5 mg/400 mg provided better analgesia than low-dose oxycodone or ibuprofen administered alone in most trials and appears to be more effective than a single dose of some other fixed-dose combination analgesics. It is generally well tolerated after single or multiple doses and short-term use is not expected to produce any of the serious adverse effects typically associated with the long-term use of opioids or NSAIDs. Thus, oxycodone/ibuprofen 5 mg/400mg is an effective, convenient treatment option for the short-term management of acute, moderate-to-severe pain.
Topics: Acute Disease; Analgesics, Non-Narcotic; Analgesics, Opioid; Area Under Curve; Clinical Trials as Topic; Drug Combinations; Drug Interactions; Humans; Ibuprofen; Oxycodone; Pain
PubMed: 16266203
DOI: 10.2165/00003495-200565160-00011 -
Medicine Aug 2022Oxycodone hydrochloride injection could be safely and effectively applied to negative pressure aspiration, and a 0.08 mg/kg dose could significantly reduce... (Randomized Controlled Trial)
Randomized Controlled Trial
Oxycodone hydrochloride injection could be safely and effectively applied to negative pressure aspiration, and a 0.08 mg/kg dose could significantly reduce postoperative uterine contraction pain of patients with dysmenorrhea.
Topics: Analgesics, Opioid; Double-Blind Method; Female; Humans; Oxycodone; Pain Measurement; Pain, Postoperative; Pelvic Pain; Treatment Outcome; Uterine Contraction
PubMed: 35984123
DOI: 10.1097/MD.0000000000030048 -
Journal of Biological Regulators and...
Topics: Cesarean Section; Female; Humans; Immune System; Oxycodone; Pain, Postoperative; Pregnancy
PubMed: 30697986
DOI: No ID Found -
International Journal of Environmental... Oct 2022Chronic low back pain (CLBP) due to osteoarthritis represents a therapeutic challenge worldwide. Opioids are extensively used to treat such pain, but the development of...
Chronic low back pain (CLBP) due to osteoarthritis represents a therapeutic challenge worldwide. Opioids are extensively used to treat such pain, but the development of tolerance, i.e., less susceptibility to the effects of the opioid, which can result in a need for higher doses to achieve the same analgesic effect, may limit their use. Animal models suggest that ultra-low doses of opioid antagonists combined with opioid agonists can decrease or block the development of opioid tolerance. In this retrospective study, we tested this hypothesis in humans. In 2019, 53 patients suffering from CLBP were treated with either Oxycodone and Naloxone Prolonged Release (27 patients, OXN patients) or Oxycodone Controlled Release (26 patients, OXY patients). The follow-up period lasted 2 years, during which 10 patients discontinued the treatment, 5 out of each group. The remaining 43 patients reached and maintained the targeted pain relief, but at 18 and 24 months, the OXY patients showed a significantly higher oxycodone consumption than OXN patients to reach the same level of pain relief. No cases of respiratory depression or opioid abuse were reported. There were no significant differences in the incidence of adverse effects between the two treatments, except for constipation, more common in OXY patients. From our results, we can affirm that a long-term opioid treatment with oxycodone-naloxone combination, when compared with oxycodone only, may significantly hinder the development of opioid tolerance. We were also able to confirm, in our cohort, the well known positive effect of naloxone in terms of opioid-induced bowel dysfunction incidence reduction.
Topics: Humans; Oxycodone; Analgesics, Opioid; Retrospective Studies; Narcotic Antagonists; Low Back Pain; Delayed-Action Preparations; Follow-Up Studies; Drug Tolerance; Naloxone; Drug Combinations; Chronic Pain
PubMed: 36293936
DOI: 10.3390/ijerph192013354