SEARCH · PubMed Health

Results for “Oxycodone”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

PubMed2006

Oxycodone for cancer-related pain: meta-analysis of randomized controlled trials.

To evaluate the efficacy and tolerability of oxycodone in cancer-related pain, we conducted a systematic review of randomized controlled trials. Four studies, comparing oral oxycodone with either oral morphine (n = 3) or oral hydromorphone (n = 1), were suitable for meta-analysis. Standardized mean differences in pain scores comparing oxycodone with control groups were pooled using random-effects models. Overall, there was no evidence that mean pain scores differed between oxycodone and control drugs (pooled standardized mean difference, 0.04; 95% confidence interval [CI], -0.29 to 0.36; P = .8; I(2) = 62%). In meta-regression analyses, pain scores were higher for oxycodone compared with morphine (0.20; 95% CI, -0.04 to 0.44) and lower compared with hydromorphone (-0.36; 95% CI, -0.71 to 0.00), although these effect sizes were small. The efficacy and tolerability of oxycodone are similar to morphine, supporting its use as an opioid for cancer-related pain.

Analgesics, Opioid↗

PubMed2005

Oxycodone vs placebo in children with undifferentiated abdominal pain: a randomized, double-blind clinical trial of the effect of analgesia on diagnostic accuracy.

BACKGROUND: Analgesics for children with acute abdominal pain are often withheld for fear that they might mask physical examination findings and thus might be unsafe. This viewpoint has been challenged recently. OBJECTIVE: To evaluate the effects of buccal oxycodone on pain relief, physical examination findings, diagnostic accuracy, and final clinical outcomes in children with acute abdominal pain. DESIGN: Prospective, randomized, double-blind, and placebo-controlled trial between December 2001 and November 2003. SETTING: University teaching hospital in Finland. Patients A total of 104 children aged 4 to 15 years with abdominal pain of less than 7 days' duration were screened, and 63 children with pain scores of 5 or higher on a 10-cm visual analog scale were eligible for the trial. Intervention Children were randomized to receive buccally either 0.1 mg/kg(-1) of oxycodone hydrochloride (n = 32) or the same volume of normal saline (n = 31). The same surgeon described the physical findings and indicated a provisional diagnosis and a provisional disposition before the children received the study medication and at 1 hour and 3.5 hours after initial dosing. Pain scores were recorded at baseline and every 30 minutes for 3.5 hours after the first study drug administration. MAIN OUTCOME MEASURES: Pain intensity difference, presence or absence of abdominal guarding, and diagnostic accuracy. RESULTS: The demographic characteristics, initial pain scores, and physical signs and symptoms were similar between the 2 groups. Both study drugs were associated with decreasing pain scores. The summed pain intensity difference over 7 observations was significantly greater in the oxycodone group, 22 +/- 18 cm, than in the placebo group, 9 +/- 12 cm (mean difference 13 cm, with a 95% confidence interval of 2-24 cm; P = .04). The diagnostic accuracy increased from 72% to 88% in the oxycodone group and remained at 84% in the placebo group after study drug administration. Laparotomy was performed in 17 patients in the oxycodone group and in 14 patients in the placebo group. Four patients without appendicitis underwent exploratory laparotomy in each group. One patient in the placebo group was initially diagnosed as having nonspecific abdominal pain, but at 14 hours, she was operated on for appendiceal perforation. CONCLUSIONS: Early administration of buccal oxycodone provides a significant pain relief to children with acute abdominal pain, without adversely altering the clinical signs or obscuring the surgical diagnosis.

Abdominal Pain↗

PubMed2005

Simultaneous determination of oxycodone and its major metabolite, noroxycodone, in human plasma by high-performance liquid chromatography.

Oxycodone (14-hydroxy-7,8-dihydrocodeinone) is a potent opioid receptor agonist. In the present study, a liquid-liquid extraction-based reversed-phase HPLC method with UV detection was validated and applied for the analysis of oxycodone and its major metabolite, noroxycodone, in human plasma. The analytes were separated using a mobile phase, consisting of acetonitrile and phosphate buffer (8:92, v/v) at a flow rate of 1 mL/min, and UV detection at 205 nm. The retention times for oxycodone, noroxycodone and codein (internal standard) were 14.7, 13.8 and 10.2 min, respectively. The validated quantitation range of the method was 2-100 ng/mL for oxycodone and 10-100 ng/mL for noroxycodone. The developed procedure was applied to assess the pharmacokinetics of oxycodone and its metabolite following administration of a single 20 mg oral dose of oxycodone hydrochloride to one healthy male volunteer.

Adult↗

PubMed2006

Cerebral kinetics of oxycodone in conscious sheep.

Oxycodone is an opioid analgesic that is administered orally or parenterally. The time-course of opioid action is a function of the systemic kinetics of the opioid, and the rate and extent of its entry into the brain and central nervous system. The latter is incompletely understood for oxycodone. Therefore, the cerebral kinetics of oxycodone was quantified using a conscious chronically instrumented sheep preparation. Five sheep were administered oxycodone as intravenous infusions (30 mg over 4 min). Using hybrid physiologically based kinetic models, cerebral kinetics was estimated from arterio-sagittal sinus concentration gradients and cerebral blood flow (CBF). A two-compartment membrane-limited model best described the data. The volume of the first brain compartment was 35.4 mL with a half-life of equilibrium of 0.6 min. The brain:blood equilibration of oxycodone was relatively slow (half-life of 7.2 min), with a large deep cerebral distribution volume (222.8 mL) for the second compartment and a moderate membrane permeability of 54.8 mL/min, which exceeded the nominal CBF (40 mL/min). Drug retention in the brain was 1.3% after 45 min. In conclusion, pharmacokinetic modelling of oxycodone showed a delayed equilibration between brain and blood of a nature that would be affected by changes in both CBF and blood brain barrier permeability.

Animals↗

PubMed2004

The use of liquid chromatography/mass spectrometry for quantitative analysis of oxycodone, oxymorphone and noroxycodone in Ringer solution, rat plasma and rat brain tissue.

Sensitive and reproducible methods for the determination of oxycodone, oxymorphone and noroxycodone in Ringer solution, rat plasma and rat brain tissue by liquid chromatography/mass spectrometry are described. Deuterated analogs of the substances were used as internal standards. Samples in Ringer solution were analyzed by direct injection of 10 microL Ringer solution diluted by an equal volume of water. The limit of quantification was 0.5 ng/mL and the method was linear in the range of 0.5-150 ng/mL for all substances. To analyze oxycodone and oxymorphone in rat plasma, 50 microL of plasma were precipitated with acetonitrile, and the supernatant was directly injected onto the column. To analyze oxycodone, oxymorphone and noroxycodone in rat plasma, 100 microL of rat plasma were subjected to a C18 solid-phase extraction (SPE) procedure, before reconstituting in mobile phase and injection onto the column. For both methods the limit of quantification in rat plasma was 0.5 ng/mL and the methods were linear in the range of 0.5-250 ng/mL for all substances. To analyze the content of oxycodone, oxymorphone and noroxycodone in rat brain tissue, 100 microL of the brain homogenate supernatant were subjected to a C18 SPE procedure. The limit of quantification of oxycodone was 20 ng/g brain, and for oxymorphone and noroxycodone 4 ng/g brain, and the method was linear in the range of 20-1000 ng/g brain for oxycodone and 4-1000 ng/g brain for oxymorphone and noroxycodone. All methods utilized a mobile phase of 5 mM ammonium acetate in 45% acetonitrile, and a SB-CN column was used for separation. The total run time of all methods was 9 min. The intra-day precision and accuracy were <11.3% and <+/-14.9%, respectively, and the inter-day precision and accuracy were <14.9% and <+/-6.5%, respectively, for all the concentrations and matrices described.

Analgesics, Opioid↗

PubMed1993

A review of oxycodone's clinical pharmacokinetics and pharmacodynamics.

Oxycodone (14-hydroxy-7,8-dihydrocodeinone) is a strong opioid agonist that is available alone or in combination with mild analgesics. It is suitable for oral administration due to high bioavailability (60%), and may also be given intramuscularly, intravenously, subcutaneously, and rectally; it is not recommended for spinal administration. In analgesic potency, oxycodone is comparable to morphine. With the exception of hallucinations, which may occur more rarely after oxycodone than after morphine, the side effects of these drugs are closely related. The abuse potential of oxycodone is equivalent to that of morphine. The usual indications for oxycodone are severe acute postoperative or posttraumatic pain and cancer pain. When oxycodone is administered, the same precautions should be taken as with morphine or other agonist opioids.

Biological Availability↗

PubMed2006

Negative urine opioid screening caused by rifampin-mediated induction of oxycodone hepatic metabolism.

INTRODUCTION: Oxycodone has become widely used in the clinic for the treatment of chronic pain. This reflects its favorable pharmacokinetics and side effect profiles. CASE REPORT: We report a 60-y-old man who had a clinically significant drug interaction between rifampin and oxycodone, resulting in 3 consecutive negative urine oxycodone screens in a 2-month period, suggesting non-adherence. A combination of urine opioid metabolite quantification by GC/MS and CYP genotyping confirmed that he was compliant with his oxycodone therapy. Determination of the complete oxycodone metabolite profile and the CYP3A4/5 and 2D6 genotype allowed the physician to be confident that the patient was compliant with the medication (and not diverting it) and to increase his oxycodone dose to optimize his pain control. CONCLUSION: This case demonstrates how the combination of analytical toxicology and pharmacogenetic analyses enhances a physician's ability to personalize drug therapy in patients with chronic pain syndromes.

Cytochrome P-450 CYP2D6↗

PubMed2004

Substance use histories in patients seeking treatment for controlled-release oxycodone dependence.

The characteristics of patients currently abusing controlled-release (CR) oxycodone admitted for inpatient detoxification were ascertained from medical record review of 48 inpatients with CR oxycodone dependence. Patients were categorized according to the manner in which they initially received the drug: illicitly or by prescription for legitimate medical use. Fifteen of the 48 patients (31%) initially obtained a CR oxycodone prescription legitimately for a medical condition. While none of these 15 patients had a history of prior opioid misuse, they were more likely than illicit CR oxycodone users to report prior detoxifications (P<0.03) as well as a lower mean age of first alcohol use (legitimate=11.7 versus illicit=14.7, P<0.05) and first illicit drug use (legitimate=12.8 versus illicit=15.8, P<0.05). These findings suggest that a history of substance abuse is common among patients abusing CR oxycodone, including individuals for whom CR oxycodone was initially legitimately prescribed for pain.

Adult↗

PubMed2004

Controlled-release oxycodone for the management of pediatric postoperative pain.

Studies addressing pain management after pediatric spinal fusion surgery have focused on the use of patient-controlled or epidural analgesia during the immediate postoperative period. Controlled-release (CR) analgesics have been found to be safe and effective in adults. The purpose of this study was to describe the use of oxycodone-CR in pediatric patients after the immediate postoperative period. A retrospective chart review of 62 postoperative spinal fusion patients (10-19 years) was conducted. The mean initial oxycodone-CR dose was 1.24 mg/kg/day. The mean ratio of conversion from parenteral morphine equivalents to oxycodone-CR was 1:1. Mean pain scores decreased from 4.2/10 to 3.7/10 with the transition to oxycodone-CR. Common side effects included dizziness, constipation, and nausea. Oxycodone-CR was used for an average of 13.3 days, which included an average wean time of 6 days. Results of this study demonstrate safe and effective use of oxycodone-CR in the pediatric spinal fusion population.

Adolescent↗

PubMed1998

Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone.

BACKGROUND: Oxycodone is metabolized in the liver by means of O-demethylation to form oxymorphone in a reaction catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). This enzyme is expressed as 2 phenotypes (extensive and poor metabolizers). Several drugs are metabolized by CYP2D6, and clinically relevant drug interactions may occur. The aim of this study was to evaluate the role of oxymorphone in mediating the opioid effects of oxycodone by means of blocking CYP2D6 with quinidine. METHODS: Ten healthy extensive metabolizers were administered 20 mg controlled-release oxycodone after premedication with placebo or 200 mg quinidine in this randomized, double-blind crossover study. A dose of 100 mg quinidine was administered 6 hours later. Plasma opioid concentrations, subjective pharmacodynamic ratings, and psychomotor function were assessed for 24 hours after drug administration. RESULTS: No oxymorphone was detected at any time after quinidine premedication in 8 of 10 subjects. Plasma oxycodone (difference not significant) and noroxycodone (P < .01) concentrations were greater after quinidine pretreatment. Prevention of the production of oxymorphone by quinidine did not affect the psychomotor or subjective drug effects of oxycodone. No difference in number of adverse effects was observed after the 2 pretreatments. CONCLUSIONS: A significant reduction in plasma oxymorphone levels did not substantially alter the pharmacodynamic effects of oxycodone. Analgesia was not evaluated because pain was not present.

Adult↗

PubMed1999

Additive analgesic effects of oxycodone and ibuprofen in the oral surgery model.

PURPOSE: A traditional approach to achieve greater analgesic efficacy is to combine an efficacious dose of a nonopioid with a dose of an opioid sufficient to produce additive analgesia without a substantial increase in the incidence of adverse effects. This study evaluated the additive analagesic effects of the combination of ibuprofen and oxycodone. PATIENTS AND METHODS: A dose of 400 mg ibuprofen was compared with 400 mg ibuprofen with oxycodone in doses of 2.5, 5, or 10 mg in the oral surgery model of acute pain. Analgesic efficacy was measured with category and visual analog scales at 15, 30, 45, and 60 minutes and hourly up to 6 hours. RESULTS: Ibuprofen plus 10 mg oxycodone produced significantly greater analgesia compared with the other three groups, as measured by the visual analog scale from 15 minutes after drug administration up to the 2-hour observation. All four treatments were similar from 3 to 6 hours, with the area under the pain intensity difference curve being similar across groups. Neither the 2.5-mg nor the 5-mg oxycodone dose provided any additive analgesia over ibuprofen at any points. Addition of oxycodone resulted in a dose-related increase in the number of patients reporting adverse effects, with significantly greater drowsiness and vomiting at the 10-mg dose. CONCLUSIONS: These results indicate that additive analgesia can be achieved for the combination of a nonsteroidal anti-inflammatory drug and an orally effective opioid, with faster onset of relief for the combination of 400 mg ibuprofen and 10 mg oxycodone over the first 2 hours after administration, but at the expense of an increased incidence of adverse events.

Adult↗

PubMed1997

The intrinsic antinociceptive effects of oxycodone appear to be kappa-opioid receptor mediated.

Our previous studies in the Sprague-Dawley rat showed that the intrinsic antinociceptive effects of oxycodone are naloxone reversible in a manner analogous to morphine but that in contrast to morphine, oxycodone's antinociceptive effects have a rapid onset of maximum effect (approximately 5-7 min compared to 30-45 min for morphine), comprise one antinociceptive phase (compared to two phases) and are of relatively short duration (approximately 90 min compared to approximately 180 min). In the present study, administration of a range of selective opioid receptor antagonists has shown that the intrinsic antinociceptive effects of oxycodone (171 nmol) are not attenuated by i.c.v. administration of (i) naloxonazine, a mu1-selective opioid receptor antagonist, or (ii) naltrindole, a delta-selective opioid receptor antagonist, in doses that completely attenuated the intrinsic antinociceptive effects of equipotent doses of the respective mu- and delta-opioid agonists, morphine and enkephalin-[D-Pen(2,5)] (DPDPE). Although beta-funaltrexamine (beta-FNA) attenuated the antinociceptive effects of oxycodone (171 nmol i.c.v.), it also attenuated the antinociceptive effects of morphine and bremazocine (kappa-opioid agonist) indicative of non-selective antagonism. Importantly, the antinociceptive effects of oxycodone (171 nmol i.c.v.) were markedly attenuated by the prior i.c.v. administration of the selective kappa-opioid receptor antagonist, norbinaltorphimine (nor-BNI), in a dose (0.3 nmol) that did not attenuate the antinociceptive effects of an equipotent dose of i.c.v. morphine (78 nmol). Taken together, these data strongly suggest that the intrinsic antinociceptive effects of oxycodone are mediated by kappa-opioid receptors, in contrast to morphine which interacts primarily with mu-opioid receptors.

Analgesics, Opioid↗

PubMed2000

Co-administration of sub-antinociceptive doses of oxycodone and morphine produces marked antinociceptive synergy with reduced CNS side-effects in rats.

Oxycodone and morphine are structurally related, strong opioid analgesics, commonly used to treat moderate to severe pain in humans. Although it is well-established that morphine is a mu-opioid agonist, this is not the case for oxycodone. Instead, our recent studies have shown that oxycodone appears to be a kappa-opioid agonist (Ross and Smith, 1997). In the current study, we now show that co-administration of sub-antinociceptive doses of oxycodone (putative kappa-opioid agonist) with morphine (mu-opioid agonist) to rats by both the intracerebroventricular and by systemic routes (intraperitoneal and subcutaneous), results in markedly increased (synergistic) levels of antinociception. Behaviourally, rats co-administered sub-antinociceptive doses of oxycodone and morphine were similar to control rats dosed with saline, whereas rats that received equi-potent doses of either opioid alone, were markedly sedated. These results suggest that co-administration of sub-analgesic doses of oxycodone and morphine to patients may provide excellent pain relief with a reduction in opioid-related CNS side-effects. Controlled clinical trials in appropriate patient populations are required to evaluate this possibility.(1)

Analgesics, Opioid↗

PubMed2001

Stability indicating HPLC method for the estimation of oxycodone and lidocaine in rectal gel.

An HPLC method for the quantification of oxycodone and lidocaine in a gel matrix is described. The mobile phase consisted of methanol--water--acetic acid (35:15:1 v/v/v) and was delivered at 1.5 ml/min through a 4.6 x 250 mm Zorbax SB-C8 column. Oxycodone was detected at 285 nm and lidocaine at 264 nm. Linear calibration curves were obtained for oxycodone in the range of 0.05--1.5% (w/w) and for lidocaine in the range of 0.1--5.0% (w/w). Oxycodone and lidocaine were treated with hydrogen peroxide and the oxidation products were readily separated on the column. The method was applied to assess the stability of a gel containing oxycodone hydrochloride (0.3% w/w) and lidocaine (1.5% w/w). The gel was stored under refrigeration in ready-to-use syringes and under these conditions oxycodone and lidocaine were stable for at least 1 year. The gel is useful in the management of tenesmus in rectal cancer.

Administration, Rectal↗

PubMed1999

Peak fronting in reversed-phase high-performance liquid chromatography: a study of the chromatographic behavior of oxycodone hydrochloride.

Severe peak asymmetry--fronting--was observed for oxycodone during elution at 30 degrees C from a C18 HPLC column using a mobile phase consisting of 14.9% MeOH, 84.5% 0.05 M KH2PO4 (pH 3.0), 0.5% MTBE, and 0.1% TEA. Investigation using deuterium-labeled oxycodone and analysis by LC/MS showed that gem diol and hemiketal adducts of oxycodone formed as a result of the equilibrium addition of water and methanol to the C-6 ketone on oxycodone. As a result of slow equilibrium kinetics at room temperature in aqueous solution, the gem-diol and methyl hemiketal eluted as an unresolved broad band in front of the oxycodone peak. Decreasing the column temperature to 0 degrees C decreased the rates of interconversion and allowed the resolution and separation of these species from each other and from oxycodone. Increasing the column temperature to 60 degrees C increased the rates of interconversion with the result that the three species eluted as a single, homogenous peak with greatly improved peak symmetry.

Analgesics, Opioid↗

PubMed1999

Efficacy and side effects of tramadol versus oxycodone for patient-controlled analgesia after maxillofacial surgery.

Tramadol, a weak opioid mu-receptor agonist, may have a favourable potency and side effect profile for intravenous patient-controlled analgesia (PCA). In a prospective, double-blind, randomized study involving 54 patients, tramadol was compared with oxycodone in PCA after maxillofacial surgery. All the patients were given diclofenac sodium 1 mg kg-1 intramuscularly and dexamethasone 8 mg twice a day. Post-operatively patients received tramadol or oxycodone by a PCA apparatus (lockout 5 min, tramadol 0.3 mg kg-1 bolus, oxycodone 0.03 mg kg-1 bolus). During the immediate recovery period, opioid was administered i.v. in a double-blind fashion, either tramadol 10 mg or oxycodone 1 mg increments until the pain control was judged to be satisfactory by the patient. Pain was assessed at rest and during activity (mouth opening) before and after loading, at 2 h after commencing the PCA, as well as at 21.00 and at 09.00 hours on the following morning. Side effects were recorded. The potency ratio of tramadol to oxycodone was found to be approximately 8:1. There was no significant difference between the groups in the VAS scores for pain. No respiratory depression was identified. Tramadol was found to provide adequate analgesia after maxillofacial surgery without risk of respiratory depression. However, the incidence of nausea was slightly greater in the tramadol group than in the oxycodone group (44% vs. 28%, NS).

Adolescent↗

PubMed2003

Conversion to oral controlled-release oxycodone from intravenous opioid analgesic in the postoperative setting.

OBJECTIVE: This study assessed conversion factors utilized by physicians to transfer postoperative patients from intravenous opioids to oral controlled-release (CR) oxycodone and the subsequent analgesic effectiveness. DESIGN: This was a multicenter, open-label, usual-use study of 189 hospitalized postoperative patients receiving opioid (usually morphine) intravenous patient-controlled analgesia (IV PCA) for at least 12 to 24 hours post-procedure. Patients who were tolerant of oral medications and without signs of paralytic ileus were converted to oral CR oxycodone, given every 12 hours for up to 7 days. RESULTS: The mean (+/-SE) conversion factor used to convert IV PCA morphine to CR oxycodone was 1.2 +/- 0.1 (N=159). The initial CR oxycodone doses, based on individual conversion factors from IV PCA morphine, produced significant reductions in pain intensity (scores <or=4) within 6 hours after the initial dose. The mean +/- SE initial dose of CR oxycodone, for patients converted from IV PCA morphine, was 27 +/- 1 mg; that for all patients was 29 +/- 2 mg. Pain at the end of the first 12 hours was controlled with these initial doses. The most common adverse events were constipation, nausea, and pruritus. CONCLUSIONS: Administered at least 12 hours following abdominal, orthopedic, or gynecologic surgery, an initial oral CR oxycodone dose calculated by multiplying the amount of IV morphine used in the previous 24 hours (immediate postoperative period) by a conversion factor of 1.2, on average, provided adequate pain control during the subsequent 12-hour dosing interval and for a maximum of 7 days. Adverse events were consistent with opioid side effects.

Administration, Oral↗

PubMed2002

Pharmacogenomics as molecular autopsy for postmortem forensic toxicology: genotyping cytochrome P450 2D6 for oxycodone cases.

Pharmacogenomics, the study of the impact of heritable traits on pharmacology and toxicology, may serve as an adjunct for certifying opioid fatalities. Oxycodone, frequently prescribed for the relief of moderate to severe pain, is metabolized by cytochrome P450 (CYP) 2D6, encoded by a polymorphic gene with three mutations (*3, *4, and *5) with a combined 95% allelic frequency and about 10% prevalence. Individuals with variant alleles are more susceptible to oxycodone toxicity. By assessing the prevalence of CYP2D6 polymorphisms and covariables, we hypothesized that oxycodone fatality may be partially due to poor drug metabolism caused by CYP2D6 variant alleles. From the Milwaukee County Medical Examiner's Office (MCMEO), a retrospective analysis of 15 oxycodone cases was followed by genotyping blood samples for the variant alleles by conventional and real-time PCRs. Institutional Review Board approval was obtained. Oxycodone, extracted from blood and/or urine, was quantitated by GC-MS. The results show two homozygous for 2D6*4 and four heterozygous for 2D6*4. The MCMEO was not significantly different from those in the control group (n = 26) (p > 0.05, Fisher's Exact Test). However, genotyping CYP2D6 provided a more definitive interpretation of the oxycodone toxicity in four cases. Therefore, pharmacogenomics may serve as an adjunct in the determination of the cause and manner of death in forensic toxicology and a pharmacogenomic algorithm for genotyping has been proposed.

Adolescent↗