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PubMed2005

Controlled-release oxycodone-induced seizures.

BACKGROUND: The use of the opioid oxycodone hydrochloride in the management of chronic pain is gaining popularity principally because of its tolerability. However, opioid-related seizure in patients with epilepsy or other conditions that may decrease seizure threshold has been described in the literature; in particular, oxycodone has been associated with seizure in a patient with acute renal failure. OBJECTIVE: The aim of this article was to report a patient with a history of seizures but normal renal and hepatic function who developed seizure on 2 occasions after oxycodone ingestion. METHODS: A 54-year-old male patient presented with a history of tonic-clonic seizures that developed immediately after intracranial surgery. Long-term treatment with carbamazepine 400 mg QD was started, and the patient was free of convulsions for approximately 7 years. The patient presented to us with severe headache that was nonresponsive to an NSAID and the opiate agonist tramadol. Treatment with controlled-release (CR) oxycodone and tramadol drops (50 mg QID if necessary) was started, and tonic-clonic seizures developed 3 days later. RESULTS: Based on laboratory analysis, the patient had normal renal and hepatic function. On discontinuation of oxycodone treatment, the seizures resolved. However, due to effective pain relief with oxycodone, the patient decided to continue treatment, and seizures recurred. Carbamazepine was then administered 4 hours before oxycodone dosing, which allowed continuation of treatment without seizure. CONCLUSIONS: A patient with a history of seizures controlled with long-term carbamazepine therapy developed seizures when he started treatment with oxycodone CR at recommended doses. Oxycodone CR should be used with extreme caution in patients with epilepsy or other conditions that may decrease seizure threshold.

Analgesics, Opioid↗

PubMed2005

Antinociceptive effect of oxycodone in diabetic mice.

The effect of oxycodone on thermal hyperalgesia in streptozotocin-induced diabetic mice was examined. The antinociceptive response was assessed by recording the latency in the tail-flick test using the radiant heat from a 50-W projection bulb on the tail. The tail-flick latency in diabetic mice was significantly shorter than that in non-diabetic mice. When diabetic mice were treated with oxycodone (5 mg/kg, s.c.), the tail-flick latency in diabetic mice was prolonged to the level considerably longer than the baseline latencies of non-diabetic mice. However, s.c. administration of morphine (5 mg/kg) did not produce a significant inhibition of the tail-flick response in diabetic mice. Oxycodone, at doses of 1.25-5.0 mg/kg administered s.c., produced a dose-dependent increase in the tail-flick latencies in both diabetic and non-diabetic mice. The antinociceptive effect of oxycodone was antagonized by pretreatment with a selective delta-opioid receptor antagonist, beta-funaltrexamine (20 mg/kg, s.c.), in both non-diabetic and diabetic mice. In non-diabetic mice, pretreatment with a selective kappa-opioid receptor antagonist, nor-binaltorphimine (20 mg/kg, s.c.) had no effect on the peak antinociceptive effect of oxycodone observed 30 min after administration, however, it slightly but significantly reduced oxycodone-induced antinociception observed 60 and 90 min after administration. On the other hand, pretreatment with nor-binaltorphimine practically abolished the peak (30 min) and persistent (60 and 90 min) antinociceptive effects of oxycodone in diabetic mice. Naltrindole (35 mg/kg, s.c.), a selective delta-opioid receptor antagonist, had no effects on the antinociceptive effect of oxycodone in both non-diabetic and diabetic mice. These results suggest that the antinociceptive effects of oxycodone may be mediated by mu- and kappa-opioid receptors in diabetic mice, whereas it may interact primarily with mu-opioid receptors in non-diabetic mice.

Analgesics, Opioid↗

PubMed2000

Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of postoperative obstetric or gynecologic pain.

OBJECTIVE: The objective of this study was to compare the effectiveness of combination hydrocodone and ibuprofen with that of combination oxycodone and acetaminophen in the treatment of moderate to severe postoperative obstetric or gynecologic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. METHODS: This randomized, double-blind, parallel-group, single-dose, active-comparator, placebo-controlled study compared the effects of a 2-tablet dose of hydrocodone 7.5 mg and ibuprofen 200 mg with those of a 2-tablet dose of oxycodone 5 mg and acetaminophen 325 mg and placebo. Analgesia was assessed over 8 hours. RESULTS: Mean pain relief (PR) scores were similar for the hydrocodone with ibuprofen and oxycodone with acetaminophen groups (n = 61 and 59, respectively) at 0.5, 1, 1.5, 2, 2.5, 3, 4, and 7 hours and significantly greater for the hydrocodone with ibuprofen group at 5, 6, and 8 hours (P < or = 0.05). Mean pain intensity difference (PID) scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen at 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours and significantly greater for hydrocodone with ibuprofen at 5, 6, 7, and 8 hours (P < or = 0.05). Total PR scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3- and 0- to 4-hour intervals and significantly greater for hydrocodone with ibuprofen for the 0- to 6- and 0- to 8-hour intervals (P < 0.05). The sum of the PID scores was similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3-, 0- to 4-, 0- to 6-, and 0- to 8-hour intervals. The median estimated time to onset of analgesia, mean peak PR score, median time to remedication, and mean global assessment score were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen. Assay sensitivity was demonstrated by the presence of statistically significant differences between both active treatments and placebo (n = 60). The number of patients experiencing adverse events was similar for each of the 3 groups (11 [18.0%], hydrocodone with ibuprofen; 7 [11.9%], oxycodone with acetaminophen; and 6 [10.0%], placebo). CONCLUSIONS: In this study, a 2-tablet dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg was as effective as a 2-tablet dose of combination oxycodone 5 mg and acetaminophen 325 mg in the treatment of moderate to severe postoperative obstetric or gynecologic pain. Both treatments were superior to placebo. The results of this study suggest that the combination of hydrocodone 7.5 mg and ibuprofen 200 mg may offer prescribers an additional option in combination pain therapy.

Acetaminophen↗

PubMed1998

The use of controlled-release oxycodone for the treatment of chronic cancer pain: a randomized, double-blind study.

To compare the effectiveness and safety of controlled-release (CR) oxycodone tablets with immediate-release (IR) oxycodone in patients with chronic cancer pain, a multicenter, randomized, double-blind, parallel-group study was performed in 111 patients with cancer pain. Patients were treated with 6 to 12 tablets or capsules of fixed-combination opioid/nonopioid analgesics per day at study entry. Patients received 30 mg of CR oxycodone tablets every 12 hr or 15 mg of IR oxycodone four times daily for 5 days. No titration or supplemental analgesic medications were permitted. The mean (+/- SE) baseline pain intensity (0 = none, 1 = slight, 2 = moderate, 3 = severe) was 1.5 +/- 0.1 for the CR oxycodone-treated group and 1.3 +/- 0.1 for the group given IR oxycodone (P > 0.05). The 5-day mean pain intensity was 1.4 +/- 0.1 and 1.1 +/- 0.1 for the CR and IR groups, respectively (P > 0.05). Discontinuation rates were equivalent (33%). There was no significant difference between treatment groups in the incidence of adverse events. This study demonstrates that cancer pain patients given 6 to 12 tablets or capsules of fixed-dose combination analgesics can be equally well treated with CR oxycodone administered every 12 hr or IR oxycodone four times daily at the same total daily dose. CR oxycodone offers the benefits of twice daily dosing.

Adult↗

PubMed2002

Oxycontin: the concept of a "ghost pill" and the postmortem tissue distribution of oxycodone in 36 cases.

Oxycodone is a semi-synthetic opioid that is structurally similar to codeine and equipotent to morphine in producing analgesic effects. Oxycodone has been prescribed in many immediate-release formulations including Percodan, Percocet, Tylox, Roxicodone, and Toxicet. In 1995, the Food and Drug Administration approved Oxycontin, a controlled-release form of oxycodone. Although the immediate-release forms of oxycodone can be prescribed in doses of 10-30 mg every 4 h, it is recommended that Oxycontin be prescribed in doses of 10-160 mg every 12 h. In a six-year period, the Los Angeles County Department of Coroner's Toxicology Laboratory detected oxycodone in 67 cases, 36 of which were determined to be the controlled-release form. The objectives of this paper are to provide general information about Oxycontin, including postmortem tissue distributions of oxycodone in cases in which the controlled-release form was identified, and to introduce the concept of ghost pills. A ghost pill is a seemingly intact but drug-free tablet that resembles an undigested pill. The isolation and identification of oxycodone from postmortem specimens was achieved using a basic, liquid-liquid extraction with screening and quantitation by gas chromatography-nitrogen-phosphorus detection and gas chromatography-mass spectrometry, respectively. Oxycodone-d3 was used as an internal standard for quantitation. The assays were linear from 0.10 to 5.0 mg/L. The tissue distribution ranges of oxycodone in the 36 case examples were heart blood 0.12-46 mg/L (36), femoral blood + < 0.10-13 mg/L (35), liver 0.11-6.1 mg/kg (16), urine 2.5-122 mg/L (22), bile 0.19-49 mg/L (15), vitreous 0.24-0.82 mg/L (6), and gastric 0.06-119 mg total (21).

Adult↗

PubMed1999

Efficacy and safety of controlled-release versus immediate-release oxycodone: randomized, double-blind evaluation in patients with chronic back pain.

OBJECTIVE: To compare the efficacy and safety of controlled-release oxycodone given every 12 hours with immediate-release oxycodone given four times daily in patients with persistent back pain. DESIGN: Randomized, double-blind, active-controlled, two-period crossover trial. PATIENTS: Fifty-seven adult outpatients with stable, chronic, moderate-to-severe low back pain despite analgesic therapy were enrolled; 47 were randomized; 11 discontinued for side effects, most commonly nausea and vomiting. INTERVENTIONS: Controlled-release oxycodone tablets given every 12 hours; immediate-release oxycodone tablets given four times daily; dose titration with controlled-release or immediate-release for up to 10 days; double-blind treatment for 4-7 days each. OUTCOME MEASURES: Patients' pain scores (0 = none, 1 = slight, 2 = moderate, 3 = severe). RESULTS: Pain intensity decreased from moderate to severe at baseline to slight at the end of titration with both oxycodone formulations. The daily oxycodone dose was 40 mg or less in 68% of patients. During double-blind treatment, mean pain intensity was maintained at 1.2 (0.1 SE) with controlled-release and at 1.1 (0.1 SE) with immediate-release oxycodone. The most common adverse events were constipation, nausea, pruritus, somnolence, and dizziness. CONCLUSIONS: Controlled-release oxycodone given every 12 hours was comparable with immediate-release oxycodone given four times daily in efficacy and safety, and it provides convenient, twice-daily, around-the-clock treatment for selected patients with persistent back pain that is inadequately controlled by nonopioids or as-needed opioid therapy.

Analgesics, Opioid↗

PubMed1993

Determination of the serum protein binding of oxycodone and morphine using ultrafiltration.

Protein binding of oxycodone and morphine in human serum was determined in vitro using ultrafiltration. Binding studies were also performed using both purified human serum albumin and human alpha 1-acid glycoprotein (AAG). Albumin was found to be the major binding protein for both oxycodone and morphine. The serum protein binding of both oxycodone and morphine was independent of drug concentration in the therapeutic range (5-100 ng/ml), but was dependent on protein concentration. In addition, bound fractions of oxycodone and morphine increased with increasing concentrations of both albumin and AAG. At physiological pH and temperature, the mean (+/- SD) serum protein binding of oxycodone was 45.1% (+/- 0.4%) and that of morphine was 35.3% (+/- 0.2%) A decrease in temperature from 37 to 23 degrees C significantly increased the serum protein binding of oxycodone and morphine by 8-9% (p < 0.0001) and 7-10% (p < 0.0001), respectively, indicating the importance of maintaining the temperature at 37 degrees C during protein binding experiments. A reduction in pH from 7.75-8.85 to 7.4 significantly reduced serum protein binding of both oxycodone and morphine by 4-5% (p < 0.0001) and 4-7% (p < 0.0001), respectively. Serum samples, to which known concentrations of oxycodone had been added and which were stored at -20 degrees C, showing a gradual but significant decline (p < 0.0001) in serum protein binding of oxycodone from approximately 45 to 39% during the 4-week storage period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗

PubMed2006

In vivo blood-brain barrier transport of oxycodone in the rat: indications for active influx and implications for pharmacokinetics/pharmacodynamics.

The blood-brain barrier (BBB) transport of oxycodone was studied in rats. Microdialysis probes were inserted into the striatum and vena jugularis. Ten animals were given a bolus dose followed by a 120-min constant rate infusion to study the steady-state concepts of oxycodone BBB equilibration. Another 10 animals were given a 60-min constant rate infusion to study the rate of equilibration across the BBB. Oxycodone-D3 was used as a calibrator for the microdialysis experiments. The samples were analyzed with a liquid chromatography-tandem mass spectrometry method and a population pharmacokinetic model was used to simultaneously fit all the data using NONMEM. A two-compartment model which allowed for a delay between the venous and arterial compartments best described the pharmacokinetics for oxycodone in blood and plasma, whereas a one-compartment model was sufficient to describe the pharmacokinetics in the brain. The BBB transport of oxycodone was parameterized as CL(in) and K(p,uu). CL(in) describes the clearance of oxycodone across the BBB into the brain, whereas K(p,uu) describes the extent of drug equilibration across the BBB. CL(in) across the BBB was estimated to 1910 microl/min x g brain. K(p,uu) was estimated to 3.0, meaning that the unbound concentration of oxycodone in brain was 3 times higher than in blood, which is an indication of active influx of oxycodone at the BBB. This is the first evidence of an opioid having an unbound steady-state concentration in brain that is higher than unity, which can explain potency discrepancies between oxycodone and other opioids.

Analgesics, Opioid↗

PubMed2006

Effect of pH on sublingual absorption of oxycodone hydrochloride.

The purpose of this study was to develop a sublingual spray drug delivery formulation of oxycodone and evaluate the effect of formulation pH on sublingual absorption of oxycodone for acute pain management using rabbit as the animal model. Using a new, sensitive, and specific liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization detector assay, the absorption bioavailability of sublingual oxycodone was determined in rabbits by comparing plasma concentration after sublingual spray delivery with equivalent intravenous dose. The effect of formulation pH on sublingual absorption of oxycodone was also tested on rabbits that had received oxycodone sublingually at a dose of 0.1 mg/0.1 mL (pH 4.0 and 9.0). Blood samples were collected at different time points, and plasma oxycodone concentrations were determined by LC/MS. Following administration of a 0.1 mg dose, the average C(max) values were found to be 64.9 +/- 12.1 and 95.2 +/- 10.1 ng/mL, for pH 4.0 and 9.0, respectively. The area under the curve (AUC) values were found to be 5807.0, and 8965.3 ng.min/mL for formulation pH 4.0 and 9.0, respectively. The mean sublingual bioavailability of oxycodone was 45.4% +/- 20.1% and 70.1% +/- 17.9%, for pH 4.0 and 9.0, respectively. The formulation pH had no significant influence on oxycodone bioavailability (P < .05). A sublingual spray dosage form of oxycodone hydrochloride would be a good alternative for fast onset pain management, especially in children.

Absorption↗

PubMed2003

A fatal drug interaction between oxycodone and clonazepam.

A case is presented of a fatal drug interaction caused by ingestion of oxycodone (Oxycontin) and clonazepam (Klonapin). Oxycodone is an opium alkaloid used in long-term pain management therapy. Clonazepam is a benzodiazepine used for the treatment of seizures and panic disorders. The Drug Abuse Warning Network (DAWN) has reported an increase of 108% in the last two years of emergency department episodes related to Oxycontin. Six billion prescriptions were written for Oxycontin in the year 2000, an 18-fold increase from four years previous (1). Oxycontin has recently gained enormous notoriety at the local and national levels; however, there are very few previously documented cases of lethal drug interactions between oxycodone and clonazepam. Synergistic effects between these two drugs are postulated to arise from different agonistic mechanisms producing similar physiological changes. It is also theorized that clonazepam may inhibit the metabolism of oxycodone. A 38-year-old white female was found dead in Jefferson County, Tennessee in March of 2001. The deceased had physical evidence of previous drug abuse and positive serological findings of hepatitis B and C. Prescription pill bottles filled under the name of the deceased, as well as another name, were found with the body. Serum, urine and gastric contents from the deceased were screened for numerous drugs and metabolites using a combination of thin layer chromatography and immunoassay techniques (EMIT and FPIA). Analysis of biological specimens from the deceased revealed the presence of: benzodiazepines, opiates (oxycodone), and trazodone metabolites in the serum; cannabinoids, benzodiazepines, opiates (oxycodone), trazodone, trazodone metabolites, nicotine, and nicotine metabolite in the urine; and benzodiazepines, opiates (oxycodone), nicotine, and nicotine metabolite in the gastric contents. Quantitative analyses for clonazepam was performed by high performance liquid chromatography (HPLC) and revealed a plasma concentration of 1.41 microg/mL. Plasma oxycodone and urine 11-nor-carboxy-delta-9-tetrahydrocannabinol concentrations were determined by gas chromatography/mass spectrometry and revealed concentrations of 0.60 microg/mL and 27.9 ng/mL, respectively. The deceased had pathologies consistent with severe central nervous system (CNS) and respiratory depression produced by high concentrations of clonazepam and oxycodone including collapsed lungs, aspirated mucus, and heart failure. The pathologies were sufficient to cause death, which was officially attributed to a drug overdose; however, the manner of death was unknown.

Adult↗

PubMed2005

One hundred seventy two deaths involving the use of oxycodone in Palm Beach County.

Oxycodone is a potent semi-synthetic narcotic prescribed for the management of pain. Previous investigators have reported that the abuse of oxycodone is most frequently seen in conjunction with the abuse of other drugs, although fatalities have been reported with oxycodone alone. We undertook a retrospective review of cases investigated by the Palm Beach County Medical Examiner's Office in which postmortem toxicologic studies indicated the presence of oxycodone. A total of 172 consecutive cases were studied, including 18 in which death was attributed to oxycodone toxicity, 117 to combined drug toxicity, 23 to trauma, 9 to natural causes and 5 to another drug or drugs. The postmortem blood concentrations of oxycodone overlapped among the groups. The mean blood oxycodone concentration among the cases of oxycodone toxicity was 0.69 mg/L, combined drug toxicity 0.72 mg/L and trauma 0.62 mg/L. Concentrations were lower in cases of deaths attributed to natural causes and to another drug or drugs (mean each 0.087 mg/L). Benzodiazepines, detected in 96 cases, were the most common co-intoxicants in the cases of combined drug toxicity, followed by cocaine, which was found in 41. The most frequently encountered benzodiazepine was alprazolam. This study confirms that deaths in which oxycodone is a factor are most commonly cases of combined drug toxicity. The high incidence of alprazolam as a co-intoxicant has not been previously recognized.

Adolescent↗

PubMedDate not supplied

Oxycodone. Pharmacological profile and clinical data in chronic pain management.

Opioids are widely used as effective analgesic therapy for cancer pain. Despite years of controversy, their use has been also accepted in chronic non-cancer pain. Oxycodone alone and in combination has been used for over 80 years in the treatment of a variety of pain syndromes. As single agent, the controlled release (CR) oxycodone's market in the USA grew from 10% in 1996 to 53% in 2000 and it has become a leading opioid in the United States. Recent data showed that the fixed-combination oxycodone/acetaminophen (5 mg/325 mg) is the most often prescribed opioid across all the different chronic pain diagnoses. Compared with morphine, oxycodone has a higher oral bioavailability and is about twice as potent. Pharmacokinetic-pharmacodynamic data support oxycodone as a pharmacologically active opiod that does not require conversion to oxymoprhone for pharmacological activity. Seven studies addressed the safety and efficacy of oxycodone for the treatment of non-cancer pain (low back pain, osteoarthritis pain, and painful diabetic neuropathy). Both immediate release (IR) and CR oxycodone are equally effective and safe. Along these trials, mean daily dosage of oxycodone was approximately 40 mg, with a low incidence of intolerable typical opiate side effects. In cancer pain, oxycodone can be considered a valid alternative to oral morphine to be used for opioid rotation. No difference in analgesic efficacy between CR oxycodone and CR morphine was found. Controlled-release preparations, with a long duration of action, are attractive because they offer the advantage of longer dosing intervals and sustained analgesic effect.

Analgesics, Opioid↗

PubMed2005

Efficacy and safety of controlled-release oxycodone and standard therapies for postoperative pain after knee or hip replacement.

BACKGROUND: Standard therapy (ST) for postoperative pain after knee and hip replacement at the Hamilton Health Sciences Henderson Hospital consists of epidural analgesia or patient-controlled analgesia for the first 48 hours, followed by oral or parenteral analgesics, or both, on an as-needed basis. We compared the efficacy and safety of scheduled controlled-release (CR) oxycodone hydrochloride (OxyContin; Purdue Pharma, Pickering, Ont.) and ST for postoperative pain 48 hours after primary knee and hip replacement. METHODS: In 2 separate 3-week studies of similar design, pain intensity, pain relief, length of hospital stay, analgesic use and side effects of CR oxycodone (n = 70) and ST (n = 101) were evaluated. In the CR oxycodone trial, a dose de-escalation protocol was used. RESULTS: At the time of discharge from hospital, patients in the CR oxycodone group recorded lower mean (and standard deviation) pain intensity scores than the ST group (20.2 [17.9] v. 27.7 [21.5] mm on a 100-mm visual analogue scale; p = 0.021). Length of hospital stay was 5.5 and 6.4 days for the CR oxycodone and ST groups respectively (p < 0.001). CR oxycodone patients used less opioid (morphine equivalent) while in hospital than ST patients (p < 0.001), and the average number of daily administrations of analgesics in hospital was 2.1 and 3.5 for CR oxycodone and ST patients respectively (p < 0.001). ST patients reported more nausea and vomiting, pruritus and fever than the CR oxycodone patients, but less somnolence, constipation, dizziness, confusion and tachycardia. CONCLUSIONS: CR oxycodone every 12 hours is as effective as ST in treating postoperative pain but length of hospital stay was shorter and analgesic administration in the hospital was used less frequently, providing potential hospital cost savings and reduced use of health care resources.

Aged↗

PubMed1980

Comparison of lysine acetylsalicylate and oxycodone in postoperative pain following upper abdominal surgery.

Intravenous lysine acetylsalicylate (LAS) and oxycodone were compared under double-blind conditions for analgesia after upper abdominal surgery in sixty patients anaesthetized by N2O--O2--halothane--relaxant technique. Either 125 mg/10 kg or 250 mg/10 kg LAS or 0.4 mg/10 kg or 0.8 mg/10 kg oxycodone was randomly administered when the patients complained of moderate or severe postoperative pain. When 30 min had elapsed following the injection of the test drug, oxycodone was given in 4 mg increments on demand until adequate pain relief was achieved. At 15 min postdrug, the lower dose of LAS offered significantly less pain relief than all other test drugs. At 30 min, the effect of the higher dose of LAS reached almost the analgesic level of the higher dose of oxycodone but only the latter provided significantly (P less than 0.05) better analgesia than the low dose of LAS. About 50% less additional narcotic supplementation was demanded following higher doses of both drugs when compared to lower ones. LAS 250 mg/10 kg (c. 1.8 g/70 kg) was found approximately equipotent to oxycodone 0.8 mg/10 kg (c. 6 mg/70 kg). However, LAS had a slower onset of action. Sweating seemed to occur more frequently after LAS than oxycodone, but significant changes in respiratory rate or sedation following LAS-oxycodone combinations when compared to oxycodone alone were not noted. The results show that for analgesia after upper abdominal surgery, 1.8 g of LAS may be substituted for about 6 mg of oxycodone.

Abdomen↗

PubMed2004

Risk of constipation in patients prescribed fentanyl transdermal system or oxycodone hydrochloride controlled-release in a California Medicaid population.

OBJECTIVE: To compare the risk of developing constipation between patients prescribed fentanyl transdermal system or oxycodone hydrochloride (HCl) controlled-release. DESIGN: California Medicaid (Medi-Cal) claims data. SETTING: Medicaid beneficiaries in California. PARTICIPANTS: Chronic pain patients who received a prescription for transdermal fentanyl or oxycodone controlled-release between October 1, 1997, and February 28, 2000, for at least three consecutive months. MAIN OUTCOME MEASURES: Constipation was defined using the International Classification of Diseases, Ninth Revision, Clinical Modification code (ICD-9-CM 564.0). The association between long-acting opioid use and constipation was determined by multivariate logistic regression after controlling for drug strength, short-acting opioid usage, and comorbidities. Odds ratios (ORs), 95% confidence intervals (CIs), and P values were reported. RESULTS: A total of 2,095 patients were included in the regression analysis (transdermal fentanyl = 877; oxycodone controlled-release = 1,218). Seventy-five patients received a constipation diagnosis (transdermal fentanyl = 28; oxycodone controlled-release = 47). Approximately 40% of patients were at least 65 years of age. Overall, oxycodone controlled-release patients had a significantly greater risk of developing constipation compared with transdermal fentanyl patients (transdermal fentanyl: n = 877; oxycodone controlled-release: n=1,218; OR = 2.55; 95% CI = 1.33-4.89; P = 0.005). Among patients who were 65 years or older, oxycodone controlled-release patients were 7.33 times more likely to be constipated than transdermal fentanyl patients (transdermal fentanyl: n = 518; oxycodone controlled-release: n = 317; OR = 7.33; 95% CI = 1.98-27.13; P = 0.003). CONCLUSION: These findings suggest that patients prescribed transdermal fentanyl may have a significantly lower risk of developing constipation compared with oxycodone controlled-release, particularly in the elderly.

Journal Article↗

PubMed2005

Oxycodone pharmacokinetics and pharmacodynamics in the rat in the presence of the P-glycoprotein inhibitor PSC833.

The objective of this study was to investigate the in vivo influence of the P-glycoprotein (P-gp) inhibitor PSC833 on the plasma pharmacokinetics, total brain concentrations and tail-flick latency of oxycodone in rats. Eight rats each received an infusion of PSC833 or vehicle without PSC833. One hour later, all animals received 0.3 mg/kg oxycodone as a 1-h infusion. Plasma samples were taken, and tail-flick latency was monitored during the infusion and for 2 h thereafter. The brains were collected at the end of the experiment. There were no differences between the two groups in area under the plasma oxycodone concentration-time curve from time zero to infinity, or oxycodone plasma clearance, volume of distribution at steady-state, or half-life. There were no differences in average total brain oxycodone concentrations at 180 min, nor were there any differences in average tail-flick latency for the PSC833 and control groups. In conclusion, coadministration of PSC833 did not alter the plasma pharmacokinetics, brain concentrations, or associated tail-flick latency of oxycodone, indicating that oxycodone is not a P-gp substrate in the rat. This has important clinical implications, as it indicates that oxycodone, unlike some other opioids, will not interact at the blood-brain barrier (BBB) with concomitantly administered P-gp substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Relative potency of controlled-release oxycodone and controlled-release morphine in a postoperative pain model.

OBJECTIVE: The relative analgesic potency of single doses of oral controlled-release oxycodone and oral controlled-release morphine were compared in a randomized, double-blind trial using a postoperative pain model. METHODS: Women (n = 169) with moderate to severe pain following abdominal hysterectomy received single oral doses of controlled-release oxycodone, 20 mg or 40 mg, or controlled-release morphine, 45 mg or 90 mg. Assessments were made at 30 min, 60 min, then hourly after dosing for 12 h or until remedication. RESULTS: The most precise estimates of relative potency showed that controlled-release oxycodone was 1.8 times more potent than controlled-release morphine for total effect (95% confidence limits 1.09-2.42; lambda 0.44) and 2.2 times more potent for peak effect (95% confidence limits 0.96-4.59; lambda 0.71). Controlled-release oxycodone at doses of 20 mg or 40 mg was comparable with controlled-release morphine at doses of 45 mg or 90 mg, respectively, for total and peak analgesic effects. For the two higher doses, time to peak relief was approximately 1 h shorter with controlled-release oxycodone than with controlled-release morphine. Most patients reported onset of analgesia within 1 h with all doses. Side effects were similar with the two opioids. CONCLUSION: Oral controlled-release oxycodone was twice as potent as oral controlled-release morphine in this single-dose, relative potency assay. When converting patients from oral morphine to oral oxycodone, an initial oral oxycodone dose of one-half the oral morphine dose is recommended.

Administration, Oral↗

PubMed2005

Comparison of the pharmacokinetics of oxycodone and noroxycodone in male dark agouti and Sprague--Dawley rats: influence of streptozotocin-induced diabetes.

PURPOSE: The aims of this study are to evaluate whether cytochrome P450 (CYP)2D1/2D2-deficient dark agouti (DA) rats and/or CYP2D1/2D2-replete Sprague-Dawley (SD) rats are suitable preclinical models of the human, with respect to mirroring the very low plasma concentrations of metabolically derived oxymorphone seen in humans following oxycodone administration, and to examine the effects of streptozotocin-induced diabetes on the pharmacokinetics of oxycodone and its metabolites, noroxycodone and oxymorphone, in both rodent strains. METHODS: High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was used to quantify the serum concentrations of oxycodone, noroxycodone, and oxymorphone following subcutaneous administration of bolus doses of oxycodone (2 mg/kg) to groups of nondiabetic and diabetic rats. RESULTS: The mean (+/-SEM) areas under the serum concentration vs. time curves for oxycodone and noroxycodone were significantly higher in DA relative to SD rats (diabetic, p<0.05; nondiabetic, p<0.005). Serum concentrations of oxymorphone were very low (<6.9 nM). CONCLUSIONS: Both DA and SD rats are suitable rodent models to study oxycodone's pharmacology, as their systemic exposure to metabolically derived oxymorphone (potent micro-opioid agonist) is very low, mirroring that seen in humans following oxycodone administration. Systemic exposure to oxycodone and noroxycodone was consistently higher for DA than for SD rats showing that strain differences predominated over diabetes status.

Alcohol Oxidoreductases↗