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PubMed2000

The effect of sedation on weaning following coronary artery bypass grafting: propofol versus oxycodone-thiopental.

BACKGROUND: Propofol has been advocated for sedation in intensive care because of superior recovery characteristics. We hypothesised that the use of two totally different sedation methods after coronary artery bypass grafting should result in differences not only in extubation time, but also in breathing pattern and gas exchange during weaning and after extubation. METHODS: Thirty patients participated in this randomised and controlled study. We used propofol infusion and oxycodone-thiopental bolus dosage, titrated to sedation level 4 or 5 according to Ramsey. Weaning was performed using protocol-based pressure support trials. RESULTS: Total (SD) fentanyl dose during operation was 33 (6) microg x kg(-1) for propofol and 34 (6) microg x kg(-1) for oxycodone-thiopental (ns). The target sedation was achieved equally with both methods. The time from admission to intensive care unit to extubation was 494 (100) min for propofol and 521 (98) min for oxycodone-thiopental (ns). Weaning times were 63 (24) min and 112 (63) min in the propofol and oxycodone-thiopental groups, respectively (P<0.05). Breathing frequency increased and tidal volume decreased from weaning to 2 h postextubation. CONCLUSION: Propofol infusion and oxycodone-thiopental bolus dosages, titrated to the same sedation end point, resulted in similar time from admission to extubation, although the weaning period was shorter in the propofol group. In terms of breathing pattern, gas exchange, blood gases and haemodynamics, the methods were similar. Propofol, despite its attractive pharmacological profile, may offer no clinical benefit in short-term sedation after a moderate dose fentanyl anaesthesia in cardiac surgery.

Carbon Dioxide↗

PubMed1990

Morphine and oxycodone hydrochloride in the management of cancer pain.

In a double-blind crossover study, morphine and oxycodone hydrochloride were administered to 20 patients who were experiencing severe cancer pain. The peroral doses were determined on the basis of patient-controlled intravenous titration. The assumed oral bioavailability ratios were 44% (group 1, first 10 patients) and 33% (group 2, last 10 patients) for morphine and 66% (group 1) and 50% (group 2) for oxycodone hydrochloride, respectively. However, the patients were able to readjust their oral dosings. Equal analgesia was achieved with both drugs, but the intravenous dose of oxycodone hydrochloride needed was 30% higher than that of morphine. The median calculated oral/intravenous ratios giving comparable analgesia were 0.31 for morphine and 0.70 for oxycodone hydrochloride. Morphine caused more nausea than oxycodone hydrochloride and hallucinations occurred only during morphine treatment. Otherwise, there were no major differences in the side effects between these two opioids.

Administration, Oral↗

PubMed2003

Comparison of sustained-release morphine with sustained-release oxycodone in advanced cancer patients.

The antinociceptive effect of morphine and oxycodone is mediated preferentially at micro and kappa receptors, respectively. The aim of this study was to evaluate the analgesic profile of the combination of morphine and oxycodone in cancer pain, compared to the standard administration of morphine alone. Controlled-release formulations of oxycodone (CRO) and morphine (CRM) were compared in 26 patients. The study started with an open-label, randomised titration phase to achieve stable pain control for 7 days, followed by a double-blind, randomised crossover phase in two periods, 14 days each. At any point, patients were allowed to use oral immediate-release morphine (IRM) as needed, in order to keep visual analogue scale < or =4. Pain, satisfaction, adverse effects and number of daily rescue morphine tablets were assessed. A total of 22 patients were evaluated. The weekly upload consumption ratio in morphine/oxycodone was 1 : 1.8 (1.80, 1.83, 1.76, 1.84). The weekly IRM consumption was higher in patients having CRM compared to patients having CRO (ratio morphine/oxycodone: 1.6, 1.6, 1.6, 1.7) (P<0.05). Patients receiving oxycodone complained of less nausea and vomiting. The rescue morphine analgesic consumption was 38% higher in patients receiving only morphine, compared to patients receiving both morphine and oxycodone. The results suggest that the combination of morphine/oxycodone (opioids with differential preferential sites of action) can be a useful alternative to morphine alone, resulting in a better analgesia profile and less emesis.

Adult↗

PubMedDate not supplied

Forensic drug testing for opiates. VI. Urine testing for hydromorphone, hydrocodone, oxymorphone, and oxycodone with commercial opiate immunoassays and gas chromatography-mass spectrometry.

Opiate testing for morphine and codeine is performed routinely in forensic urine drug-testing laboratories in an effort to identify illicit opiate abusers. In addition to heroin, the 6-keto-opioids, including hydromorphone, hydrocodone, oxymorphone, and oxycodone, have high abuse liability and are self-administered by opiate abusers, but only limited information is available on detection of these compounds by current immunoassay and gas chromatographic-mass spectrometric (GC-MS) methods. In this study, single doses of hydromorphone, hydrocodone, oxymorphone, and oxycodone were administered to human subjects, and urine samples were collected before and periodically after dosing. Opiate levels were determined in a quantitative mode with four commercial immunoassays, TDx opiates (TDx), Abuscreen radioimmunoassay (ABUS), Coat-A-Count morphine in urine (CAC), and EMIT d.a.u. opiate assay (EMIT), and by GC-MS. GC-MS assay results indicated that hydromorphone, hydrocodone, oxymorphone, and oxycodone administration resulted in rapid excretion of parent drug and O-demethylated metabolites in urine. Peak concentrations occurred within 8 h after drug administration and declined below 300 ng/mL within 24-48 h. Immunoassay testing indicated that hydromorphone, hydrocodone, and oxycodone, but not oxymorphone, were detectable in urine by TDx and EMIT (300-ng/mL cutoff) for 6-24 h. ABUS detected only hydrocodone, and CAC failed to detect any of the four 6-keto-opioid analgesics. Generally, immunoassays for opiates in urine displayed substantially lower sensitivities for 6-keto-opioids compared with GC-MS. Consequently, urine samples containing low to moderate concentrations of hydromorphone, hydrocodone, oxymorphone, and oxycodone will likely go undetected when tested by conventional immunoassays.

Enzyme Multiplied Immunoassay Technique↗

PubMedDate not supplied

The detection of oxycodone in meconium specimens.

A procedure for the determination of oxycodone in meconium using direct ELISA microplate technology followed by electron impact gas chromatography-mass spectrometry (GC-MS) is described for the first time. The abuse of oxycodone (OxyContin) has been widely discussed in mainstream media, and it has been described as a cheap form of heroin. Oxycodone has been reported as having a high degree of abuse and potential complications in neonates from maternal drug use. Using a standard enzyme multiplied immunoassay screening technology, the cross-reactivity of oxycodone to the morphine antibody is only 5-6%. A positive screening value would require a high concentration of drug to be present, so a protocol for the detection of oxycodone in meconium using a direct ELISA microplate immunoassay followed by GC-MS was developed. The assay is now routinely used in our laboratory.

Cross Reactions↗

PubMed1993

Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo.

In a double-blind randomized crossover trial, oxycodone or placebo was given in divided night-time doses to 11 patients with idiopathic restless legs syndrome (RLS) for 2 weeks prior to appropriate polysomnographic studies. Under double-blinded conditions, patients were asked to do daily ratings of their leg sensations, motor restlessness and daytime alertness on a 1-4 scale for the 2 weeks prior to the polysomnographic studies and for the nights of the polysomnographic studies as well. Leg sensations (p < 0.009), motor restlessness (p < 0.006) and daytime alertness (p < 0.03) were significantly improved on oxycodone as compared to baseline or placebo. Patients were studied polysomnographically under double-blinded conditions for 2 nights in each phase of the protocol. On an average dose of 15.9 mg oxycodone (equivalent to approximately three 5-mg tablets of commercial preparation), there was a statistically significant reduction in the number of periodic limb movements in sleep [(PLMS)/hour sleep (p < 0.004)] and in the number of arousals/hour sleep (p < 0.009) on drugs as compared to baseline or placebo. A statistically significant improvement was also noted in sleep efficiency (p < 0.006) and 10 of the 11 patients preferred oxycodone over placebo. We conclude that oxycodone is an effective treatment for RLS and PLMS.

Adult↗

PubMed1991

Quantitation of oxycodone in human plasma using high-performance liquid chromatography with electrochemical detection.

An original, highly sensitive and specific high-performance liquid chromatographic (HPLC) assay has been developed for the measurement of oxycodone in human plasma with a detection limit of 10 ng/ml using a 1.0-ml plasma sample. Plasma samples were initially acid-washed and then extracted twice at pH 10 with butyl chloride. Oxycodone and codeine (internal standard) were eluted with a mixture of methanol, acetonitrile, and 0.01 M pH 7 phosphate buffer to which 40 mg/l of cetyltrimethylammonium bromide (cetavlon) was added at ambient temperature and detected with electrochemical detection. The addition of cetavlon to the mobile phase markedly reduced the interaction between oxycodone and Si-OH groups on the stationary phase of the HPLC column, so that the organic content of the mobile phase could be reduced from 80 to 25%. Quantitation was achieved using the peak height ratio of oxycodone to codeine. The assay is currently being used for the study of oxycodone pharmacokinetics after single oral doses of 10 and 20 mg and single rectal doses of 30 mg.

Administration, Oral↗

PubMedDate not supplied

Treatment of persistent pain associated with osteoarthritis with controlled-release oxycodone tablets in a randomized controlled clinical trial.

OBJECTIVE: This study, lasting up to 90 days, was undertaken in patients with osteoarthritis with persistent moderate to severe pain uncontrolled by standard therapy (nonsteroidal anti-inflammatory drugs, acetaminophen, and/or short-acting opioids) to evaluate functional outcomes, as well as efficacy and safety, of controlled-release oxycodone versus placebo. METHODS: One hundred seven patients received either controlled-release oxycodone or placebo every 12 hours in this double blind, randomized, placebo-controlled, parallel-group study. Stable previous regimens of acetaminophen or nonsteroidal anti-inflammatory agents were allowed to continue. Primary efficacy variables included Brief Pain Inventory average pain intensity scores at completion of initial titration, Western Ontario and McMaster Universities Osteoarthritis Index scores at days 30 and 60, and the percentage of patients discontinuing due to inadequate pain control. RESULTS: Controlled-release oxycodone was significantly superior to placebo in decreasing average pain intensity and in reducing pain-induced interference with general activity, walking ability (except at day 30), and normal work, as well as mood, sleep, relations with people (at days 60 and 90), and enjoyment in life. Daily functioning, as measured by the Western Ontario and McMaster Universities Osteoarthritis Index, was also significantly improved in the controlled-release oxycodone group. In the placebo group, a significantly greater percentage of patients discontinued due to inadequate pain control. Adverse events were consistent with opioid adverse events, and no safety concerns were noted. DISCUSSION: Treatment with controlled-release oxycodone of patients with osteoarthritis with persistent moderate to severe pain uncontrolled by standard therapy resulted in significant pain control and improvements in physical functioning.

Aged↗

PubMed1998

Comparison of analgesic efficacy of oxycodone and morphine in postoperative intravenous patient-controlled analgesia.

BACKGROUND: Morphine has been the standard opioid in patient-controlled analgesia (PCA). Oxycodone, the analgesic potency of which in i.v. administration has been suggested to be slightly greater than that of morphine, has not yet been studied for its efficacy in PCA. METHODS: Fifty patients, undergoing a plastic reconstruction of the breast or a major operation of the vertebrae, such as lumbar spinal fusion, used PCA for postoperative pain. Patients were randomized to receive either morphine 45 microg/kg or oxycodone 30 microg/kg as i.v. bolus doses. Patients were assessed for pain with a visual analogue scale (VAS) and side effects at 3, 9 and 24 h. Venous blood samples for the measurement of plasma concentration of oxycodone and that of morphine and its metabolites were taken. RESULTS: In this study patients needed, on average, the same amount of oxycodone and morphine in the recovery room and on the ward. There was no difference in the quality of analgesia (VAS) or incidence of side effects, such as nausea, vomiting, pruritus and urinary retention. The plasma concentrations of morphine-6-glucuronide showed that this metabolite might contribute to the analgesia resulting from morphine administration. CONCLUSIONS: The same dose of intravenous oxycodone and morphine administered by PCA pump was needed for immediate postoperative analgesia. The two drugs appear to be equipotent.

Adult↗

PubMed1992

Antinociceptive effects and central nervous system depression caused by oxycodone and morphine in rats.

Antinociception and central nervous system depression (CNSD) caused by intraperitoneal, intrathecal and subcutaneous administration of oxycodone or morphine were studied in a randomized and blind, saline controlled study in rats. Antinociception was assessed with the tail-flick and hot plate tests. CNSD was assessed by testing the corneal, placing and righting reflexes and with a 4-point catalepsy score. Intraperitoneally and subcutaneously administered oxycodone and morphine were given in doses of 2.5-10 and 5-20 mg kg-1 respectively. The intrathecal doses were 12.5 micrograms and 100 micrograms of oxycodone and 6.25 micrograms and 50 micrograms of morphine. In both nociceptive tests subcutaneously and intraperitoneally administered oxycodone was 2-4 times more potent than morphine, while intrathecal morphine was over 14 times more potent. CNSD was more profound with oxycodone than with morphine after intraperitoneal and subcutaneous administration, but was not observed after intratechal administration of either drug. Differences in opioid receptor affinities, liposolubilities and metabolism are discussed as possible explanations.

Analgesics↗

PubMed2006

Trends in controlled-release oxycodone (OxyContin) prescribing among Medicaid recipients in Kentucky, 1998-2002.

CONTEXT: Prescription opioid abuse has emerged as a public health problem, particularly in rural America. PURPOSE: To examine temporal and geographic trends in rates of controlled-release oxycodone (OxyContin) prescribing for Kentucky Medicaid recipients. METHODS: A cross-sectional analysis was completed in which the state was divided into 3 regions (distressed Appalachia, Appalachia, and other Kentucky), and data from Medicaid pharmacy claims from 1998 to 2002 were analyzed. Claims were further stratified by disability status. FINDINGS: Temporary Assistance for Needy Families Medicaid recipients in distressed Appalachia were more likely than those in other Kentucky regions to file controlled-release oxycodone claims in 1999, 2001, and 2002. Even after adjusting for the proportion of Temporary Assistance for Needy Families recipients in each region, the distressed region still had significantly higher rates (P< .05) than the non-Appalachian region of controlled-release oxycodone prescription claims among Temporary Assistance for Needy Families recipients. Similar findings were observed for disabled Medicaid recipients in 2002. CONCLUSIONS: Higher rates of claims for controlled-release oxycodone in the distressed Appalachian region of Kentucky suggest that economic and health factors unique to this area may be contributing to increased use of this product. The increased availability of controlled-release oxycodone in distressed Appalachian regions may facilitate abuse.

Analgesics, Opioid↗

PubMed2004

Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes.

Oxycodone undergoes N-demethylation to noroxycodone and O-demethylation to oxymorphone. The cytochrome P450 (P450) isoforms capable of mediating the oxidation of oxycodone to oxymorphone and noroxycodone were identified using a panel of recombinant human P450s. CYP3A4 and CYP3A5 displayed the highest activity for oxycodone N-demethylation; intrinsic clearance for CYP3A5 was slightly higher than that for CYP3A4. CYP2D6 had the highest activity for O-demethylation. Multienzyme, Michaelis-Menten kinetics were observed for both oxidative reactions in microsomes prepared from five human livers. Inhibition with ketoconazole showed that CYP3A is the high affinity enzyme for oxycodone N-demethylation; ketoconazole inhibited >90% of noroxycodone formation at low substrate concentrations. CYP3A-mediated noroxycodone formation exhibited a mean K(m) of 600 +/- 119 microM and a V(max) that ranged from 716 to 14523 pmol/mg/min. Contribution from the low affinity enzyme(s) did not exceed 8% of total intrinsic clearance for N-demethylation. Quinidine inhibition showed that CYP2D6 is the high affinity enzyme for O-demethylation with a mean K(m) of 130 +/- 33 microM and a V(max) that ranged from 89 to 356 pmol/mg/min. Activity of the low affinity enzyme(s) accounted for 10 to 26% of total intrinsic clearance for O-demethylation. On average, the total intrinsic clearance for noroxycodone formation was 8 times greater than that for oxymorphone formation across the five liver microsomal preparations (10.5 microl/min/mg versus 1.5 microl/min/mg). Experiments with human intestinal mucosal microsomes indicated lower N-demethylation activity (20-50%) compared with liver microsomes and negligible O-demethylation activity, which predict a minimal contribution of intestinal mucosa in the first-pass oxidative metabolism of oxycodone.

Aryl Hydrocarbon Hydroxylases↗

PubMed2004

Establishing the dosage equivalency of oxymorphone extended release and oxycodone controlled release in patients with cancer pain: a randomized controlled study.

OBJECTIVE: To compare the analgesic efficacy and safety of oxymorphone extended release (ER) and oxycodone controlled release (CR) in patients with moderate to severe cancer pain. RESEARCH DESIGN AND METHODS: This randomized, multicenter, double-blind, 2-period crossover study included adult outpatients (>or= 18 years of age) with moderate or severe cancer pain who were first titrated for 3-10 days with open-label oxymorphone or oxycodone to achieve a stable dose that provided and other efficacy parameters were comparable for adequate analgesia with tolerable adverse events and no requirement for more than 2 doses of rescue medication per day. The subsequent double-blind treatment phase was a 7- to 10-day period of oxycodone CR or oxymorphone ER treatment followed by crossing over to the alternate medication for another 7-10 days. During the treatment phase, up to 2 doses per day of morphine sulfate 15-mg tablets were allowed as rescue. MAIN OUTCOMES AND MEASURES: Assessments included the Brief Pain Inventory, global evaluations, Karnofsky performance status, and clinical laboratory evaluations (serum chemistry profile, complete blood count, urinalysis). Efficacy variables were analyzed using a mixed-effects model with treatment, sequence, and period as fixed effects and subject as a random effect. RESULTS: Forty-seven patients entered the titration/stabilization phase, 44 received at least 1 dose of study drug, 42 completed the first double-blind phase, and 40 completed the second double-blind phase. Mean pain intensity scores the 2 groups. The mean daily dosage of oxycodone CR (91.9 mg) was twice that of oxymorphone ER (45.9 mg), an equianalgesic dose ratio of 2:1. Rescue medication use was low in both groups (approximately 1 tablet of morphine sulfate 15 mg/day). No significant differences in opioid adverse events were observed between the groups. CONCLUSIONS: Adult patients with cancer who were taking oxycodone CR were readily converted to oxymorphone ER and required half the milligram dose to stabilize their pain. Within 72 h, most patients achieved a stable dose that provided adequate relief with similar opioid adverse events.

Adult↗

PubMed2006

Morphine, oxycodone, methadone and its enantiomers in different models of nociception in the rat.

We studied the effects of the commonly used mu-opioid receptor agonists morphine, oxycodone, methadone and the enantiomers of methadone in thermal and mechanical models of acute pain and in the spinal nerve ligation model of neuropathic pain in rats. Subcutaneous administration of morphine, oxycodone, and methadone produced a dose-dependent antinociceptive effect in the tail flick, hotplate, and paw pressure tests. l-methadone, racemic methadone, and oxycodone had a similar dose-dependent antinociceptive effect, whereas the dose-response curve of morphine was shallower. In the spinal nerve ligation model of neuropathic pain, subcutaneous administration of morphine, oxycodone, methadone and l-methadone had antiallodynic effects in tests of mechanical and cold allodynia. l-methadone showed the strongest antiallodynic effect of the tested drugs. d-methadone was inactive in all tests. Morphine 5.0 mg/kg, oxycodone 2.5 mg/kg, and l-methadone 1.25 mg/kg decreased spontaneous locomotion 30 min after drug administration. In conclusion, in acute nociception all mu-opioid receptor agonists produced antinociception, with morphine showing the weakest effect. In nerve injury pain, l-methadone showed the greatest antiallodynic potency in both mechanical and cold allodynia compared with the other opioids. Opioids seem to have different profiles in different pain models. l-methadone should be studied for neuropathic pain in humans.

Acute Disease↗

PubMed1982

Determination of oxycodone metabolites in urines and feces of several mammalian species.

Determination of oxycodone metabolites excreted in urines and feces of several mammalian species was studied by use of the tritium labeled compound. It was found that the radioactivity was excreted more in the urines than in the feces in rabbits, guinea pigs and mice, but not in rats, who eliminated it equally into the urines and feces. Most of the radioactivity was excreted in 48 h after the administration. Seven metabolites, oxymorphone, 6 alpha-oxycodol, 6 beta-oxycodol, 7 beta-hydroxy-6 beta-oxycodol, noroxycodone, oxycodone N-oxide, and 6 alpha-oxycodol, N-oxide, as well as well as unchanged oxycodone, were found to be excreted into urines of rabbits in both free and conjugated forms except two N-oxides, which were found only in the free form. It was discussed that analgesic effect of oxycodone would mainly be attributable to the oxycodone itself, but not to the metabolites.

Animals↗

PubMed2004

Oxycodone intoxication in an infant: accidental or intentional exposure?

A case is presented of a 10 month old male who went into cardiac arrest at a local store. The infant subsequently expired and was autopsied at the Office of the Chief Medical Examiner, State of Maryland. The only remarkable finding was the detection of oxycodone in the postmortem specimens; the blood and liver oxycodone concentrations were 0.6 mg/L and 1.6 mg/kg, respectively. Oxycodone was identified and quantitated by gas chromatography-nitrogen-phosphorus detection and confirmed by full scan electron ionization gas chromatography-mass spectrometry. The medical examiner ruled that the cause of death was oxycodone intoxication, and the manner of death was homicide. The key toxicologic question in this case was whether or not it was reasonable for the infant to be exposed to oxycodone exclusively through breast milk or through an alternate source. It was concluded that, at best, there were serious concerns about the likelihood of drug exposure through consumption of breast milk.

Analgesics, Opioid↗

PubMed2000

Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain: placebo-controlled trial and long-term evaluation.

BACKGROUND: Although opioid analgesics have well-defined efficacy and safety in treatment of chronic cancer pain, further research is needed to define their role in treatment of chronic noncancer pain. OBJECTIVE: To evaluate the effects of controlled-release oxycodone (OxyContin tablets) treatment on pain and function and its safety vs placebo and in long-term use in patients with moderate to severe osteoarthritis pain. METHODS: One hundred thirty-three patients experiencing persistent osteoarthritis-related pain for at least 1 month were randomized to double-blind treatment with placebo (n = 45) or 10 mg (n = 44) or 20 mg (n = 44) of controlled-release oxycodone every 12 hours for 14 days. One hundred six patients enrolled in an open-label, 6-month extension trial; treatment for an additional 12 months was optional. RESULTS: Use of controlled-release oxycodone, 20 mg, was superior (P<.05) to placebo in reducing pain intensity and the interference of pain with mood, sleep, and enjoyment of life. During long-term treatment, the mean dose remained stable at approximately 40 mg/d after titration, and pain intensity was stable. Fifty-eight patients completed 6 months of treatment, 41 completed 12 months, and 15 completed 18 months. Common opioid side effects were reported, several of which decreased in duration as therapy continued. CONCLUSIONS: Around-the-clock controlled-release oxycodone therapy seemed to be effective and safe for patients with chronic, moderate to severe, osteo-arthritis-related pain. Effective analgesia was accompanied by a reduction in the interference of pain with mood, sleep, and enjoyment of life. Analgesia was maintained during long-term treatment, and the daily dose remained stable after titration. Typical opioid side effects were reported during short- and long-term therapy.

Aged↗

PubMed2001

Identification of ozone-oxidation products of oxycodone by electrospray ion trap mass spectrometry.

The products of oxycodone oxidized by ozone were characterized by electrospray ionization-tandem mass spectrometry (ESI--MS/MS). Liquid Chromatography(LC)--MS analyses revealed that the main constituents in the oxidation reaction mixture included the protonated molecules m/z 316, corresponding to oxycodone, and m/z 332, m/z 348, m/z 366, corresponding to the oxidation products. ESI--MS/MS and MS(n) spectra were used to study oxycodone fragmentation in detail and to characterize the structures of oxidation products. The results show that the oxidation products were formed by addition of one or two oxygen atoms or by addition of three oxygen and two hydrogen atoms to oxycodone. The fragmentation of the oxidation products also shows that the aromatic ring oxidizes due to rupture of the C-3--C-4 bond during product formation.

Drug Stability↗