Oxycodone :: administration & dosage
Latest Paper:
Imai Satoshi,
Minoru Narita,
Ayumi Ozeki,
Atsushi Nakamura,
Seiko Hashimoto,
Michiko Narita,
Naoko Kuzumaki,
Yasuhito Uezono,
Tsutomu Suzuki
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
In the present study, we demonstrated that repeated treatment with fentanyl, but not morphine or oxycodone, causes a rapid desensitization to its ability to block the hyperalgesia associated with the attenuation of mu-opioid receptor resensitization in mice in a chronic pain-like state. In contrast, no such effect was noted in beta-endorphin knockout mice under the chronic pain-like conditions. On the assumption that beta-endorphin might be released within the spinal cord under pain-like conditions, we further examined whether beta-endorphin could be responsible for a desensitization and resensitization of fentanyl under the chronic pain. In cultured cells, unlike morphine, fentanyl and oxycodone induced a robust mu-opioid receptor internalization and, in turn, its resensitization. In the presence of beta-endorphin, the internalized mu-opioid receptor induced by fentanyl, but not oxycodone, remained within the cytosolic component even after washing out. The findings suggest that beta-endorphin could attenuate the resensitization of mu-opioid receptors. This phenomenon may explain the high degree of tolerance to fentanyl that develops with hyperalgesia caused by a chronic pain-like state.
Mesh-terms: Analgesics, Opioid :: administration & dosage; Analgesics, Opioid :: therapeutic use; Animals; Chronic Disease; Disease Models, Animal; Drug Tolerance :: genetics; Fentanyl :: administration & dosage; Fentanyl :: therapeutic use; Humans; Mice; Morphine :: administration & dosage; Morphine :: therapeutic use; Oxycodone :: administration & dosage; Oxycodone :: therapeutic use; Pain :: drug therapy; Receptors, Opioid, mu :: physiology; beta-Endorphin :: physiology; beta-Endorphin :: secretion;
Most cited papers:
Department of Medicine, University of Toronto, Ontario, Canada.
OBJECTIVE: Although opioid analgesics are used in the management of neuropathic pain syndromes, evidence of their efficacy remains to be established. We evaluated the clinical efficacy and safety of oxycodone in neuropathic pain using postherpetic neuralgia as a model. METHODS: Patients with postherpetic neuralgia of at least moderate intensity were randomized to controlled-release oxycodone 10 mg or placebo every 12 hours, each for 4 weeks, using a double-blind, crossover design. The dose was increased weekly up to a possible maximum of 30 mg every 12 hours. Pain intensity and pain relief were assessed daily, and steady (ongoing) pain, brief (paroxysmal) pain, skin pain (allodynia), and pain relief were recorded at weekly visits. Clinical effectiveness, disability, and treatment preference were also assessed. RESULTS: Fifty patients were enrolled and 38 completed the study (16 men, 22 women, age 70+/-11 years, onset of postherpetic neuralgia 31+/-29 months, duration of pain 18+/-5 hours per day). The oxycodone dose during the final week was 45+/-17 mg per day. Compared with placebo, oxycodone resulted in pain relief (2.9+/-1.2 versus 1.8+/-1.1, p= .0001) and reductions in steady pain (34+/-26 versus 55+/-27 mm, p= .0001), allodynia (32+/-26 versus 50+/-30 mm, p= .0004), and paroxysmal spontaneous pain (22+/-24 versus 42+/-32 mm, p= .0001). Global effectiveness, disability, and masked patient preference all showed superior scores with oxycodone relative to placebo (1.8+/-1.1 versus .7+/-1. , p= .0001; .3+/- .8 versus .7+/-1. , p= .041; 67% versus 11%, p= .001, respectively). CONCLUSIONS: Controlled-release oxycodone is an effective analgesic for the management of steady pain, paroxysmal spontaneous pain, and allodynia, which frequently characterize postherpetic neuralgia.
Mesh-terms: Aged; Analgesics, Opioid :: administration & dosage; Analgesics, Opioid :: adverse effects; Analgesics, Opioid :: therapeutic use; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Female; Herpes Zoster :: complications; Human; Male; Middle Aged; Neuralgia :: drug therapy; Neuralgia :: physiopathology; Neuralgia :: virology; Oxycodone :: administration & dosage; Oxycodone :: adverse effects; Oxycodone :: therapeutic use; Pain :: physiopathology; Support, Non-U.S. Gov't; Treatment Outcome;
University of Toronto, Toronto, ON, Canada. peter.watson@utoronto.ca
BACKGROUND: Painful neuropathy is one of the most common long-term complications of diabetes mellitus and often proves difficult to relieve.METHODS: Patients with diabetic neuropathy with moderate or greater pain for at least 3 months, were evaluated for efficacy, safety and health-related quality of life (QOL) while receiving controlled-release (CR) oxycodone (OxyContin) or active placebo. Patients underwent washout from all opioids 2-7 days before randomization to 10 mg CR oxycodone or active placebo ( .25 mg benztropine) q12h. The dose was increased, approximately weekly, to a maximum of 40 mg q12h CR oxycodone or 1 mg q12h benztropine, with crossover to the alternate treatment after a maximum of 4 weeks. Acetaminophen, 325-650 mg q4-6h prn was provided as rescue.RESULTS: Thirty-six patients were evaluable for efficacy (21 men, 15 women, mean age 63. +/-9.4 years). CR oxycodone resulted in significantly lower (P= .0001) mean daily pain (21.8+/-20.7 vs. 48.6+/-26.6 mm VAS), steady pain (23.5+/-23. vs. 47.6+/-30.7 mm VAS), brief pain (21.8+/-23.5 vs. 46.7+/-30.8 mm VAS), skin pain (14.3+/-20.4 vs. 43.2+/-31.3 mm VAS), and total pain and disability (16.8+/-15.6 vs. 25.2+/-16.7; P= .004). Scores from 6 of the 8 SF-36 domains and both summary scales, Standardized Physical Component (P= .0002) and Standardized Mental Component (P= .0338) were significantly better during CR oxycodone treatment. The number needed to treat to obtain one patient with at least 50% pain relief is 2.6 and clinical effectiveness scores favoured treatment with CR oxycodone over placebo (P= .0001).CONCLUSION: CR oxycodone is effective and safe for the management of painful diabetic neuropathy and improves QOL.
Mesh-terms: Aged; Analgesics, Opioid :: administration & dosage; Analgesics, Opioid :: adverse effects; Cross-Over Studies; Delayed-Action Preparations; Diabetic Neuropathies :: drug therapy; Diabetic Neuropathies :: physiopathology; Diabetic Neuropathies :: psychology; Disability Evaluation; Double-Blind Method; Female; Human; Male; Mental Health; Middle Aged; Oxycodone :: administration & dosage; Oxycodone :: adverse effects; Pain Measurement; Placebos; Skin :: physiopathology; Support, Non-U.S. Gov't;
Department of Anaesthesia, Helsinki University, Finland.
1. The pharmacokinetics and metabolism of oxycodone were studied in nine healthy young volunteers in a cross-over study. Each subject received oxycodone chloride once intramuscularly ( .14 mg kg-1) and twice orally ( .28 mg kg-1) at intervals of 2 weeks. A double-blind randomized pretreatment with amitriptyline (10-50 mg a day) or placebo was given prior to oral oxycodone. 2. The concentrations of oxycodone, noroxycodone and oxymorphone in plasma and the 24 h urine recoveries of their conjugated and unconjugated forms were measured by gas chromatography. 3. No differences were found between treatments in mean Cmax and AUC values of oxycodone which varied from 34 to 38 ng ml-1 and from 208 to 245 ng ml-1 h, respectively. The median tmax of oxycodone was 1 h in all groups. The bioavailability of oral relative to i.m. oxycodone was 60%. The mean renal clearance of oxycodone was .07- .08 l min-1. The kinetics of oxycodone were unaffected by amitriptyline. 4. The mean ratio of the AUC( .24 h) values of unconjugated noroxycodone to oxycodone was .45 after i.m. oxycodone and .6- .8 after oral oxycodone. Plasma oxymorphone concentrations were below the limit of the assay. Eight to 14% of the dose of oxycodone was excreted in the urine as unconjugated and conjugated oxycodone over 24 h. Oxymorphone was excreted mainly as a conjugate whereas noroxycodone was recovered mostly in an unconjugated form.
Mesh-terms: Administration, Oral; Adult; Amitriptyline :: administration & dosage; Chromatography, Gas; Double-Blind Method; Female; Human; Injections, Intramuscular; Male; Morphinans :: blood; Morphinans :: urine; Oxycodone :: administration & dosage; Oxycodone :: metabolism; Oxycodone :: pharmacokinetics; Oxymorphone :: blood; Oxymorphone :: urine; Placebos; Reference Values; Support, Non-U.S. Gov't;
Purdue Frederick Company, Norwalk, CT 06850-3590, USA.
Plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined after administration of 20 mg oral controlled-release oxycodone tablets to four subject groups: young (aged 21 to 45 years) men, elderly (aged 65 to 79 years) men, young women, and elderly women. Area under the oxycodone and noroxycodone concentration-time curve (AUC) values were comparable among the four groups. Compared with oxycodone, the oxymorphone AUC values were small, with significant differences between subject groups. AUC values were also calculated for the pharmacodynamic variable "drug effect," scored on a 100 mm visual analog scale. The two groups with the highest oxycodone AUC values (young and elderly women) had the lowest oxymorphone AUC values and the greatest drug effect AUC values. The two groups with the lowest oxycodone AUC values (young and elderly men) had the highest oxymorphone AUC values and the lowest drug effect AUC values. These results support oxycodone, and not oxymorphone, as being primarily responsible for pharmacodynamic and analgesic effects.
Mesh-terms: Administration, Oral; Adult; Aged; Analgesics, Opioid :: administration & dosage; Analgesics, Opioid :: blood; Analgesics, Opioid :: pharmacokinetics; Analgesics, Opioid :: pharmacology; Delayed-Action Preparations; Female; Human; Male; Morphinans :: administration & dosage; Morphinans :: blood; Morphinans :: pharmacokinetics; Morphinans :: pharmacology; Oxycodone :: administration & dosage; Oxycodone :: blood; Oxycodone :: pharmacokinetics; Oxycodone :: pharmacology; Oxymorphone :: administration & dosage; Oxymorphone :: blood; Oxymorphone :: pharmacokinetics; Oxymorphone :: pharmacology; Reference Values; Support, Non-U.S. Gov't;
Department of Anaesthesia, Helsinki University Central Hospital, Finland.
In order to evaluate postoperative pain treatment following thoracic surgery, 214 medical records of patients who were operated during 1986-1988 were examined. Nurses' comments concerning pain and the amounts of analgesics given during the 2 postoperative days were recorded. The 150 patients who were still alive in December 1989 were sent a postal questionnaire which asked about the pain and the efficacy of pain relief they had received after their operation. They were also asked if they still had pain which they connected to the thoracotomy and if any attempts had been made to treat that pain. The mean consumption of intramuscular oxycodone was 38 mg during the 1st and 33 mg during the 2nd postoperative day. The administration of nonsteroidal anti-inflammatory drugs significantly reduced the opioid consumption on the second but not on the first postoperative day. In 30% of the patients' charts there were no remarks on pain, in 10% there was a mention of no pain, in 40% pain was mentioned and in 20% the patient was reported to have severe pain. During the first postoperative week little pain was experienced by 60% of the patients, considerable pain by 35% and excruciating pain by 5% of the patients being interviewed. The postoperative pain relief was rated as good in 60% of the answers, satisfactory in 38% and poor in 2%. Persistent post-thoracotomy pain lasting for more than 6 months was reported by 44% of the patients, of whom 66% had received treatment for the pain.
Mesh-terms: Acute Disease; Anesthesia Recovery Period; Anesthesia, Conduction; Anesthesia, Epidural; Benzilates :: administration & dosage; Benzilates :: therapeutic use; Benzophenones :: administration & dosage; Benzophenones :: therapeutic use; Chronic Disease; Diclofenac :: administration & dosage; Diclofenac :: therapeutic use; Dipyrone :: administration & dosage; Dipyrone :: therapeutic use; Drug Combinations; Female; Finland :: epidemiology; Human; Incidence; Indomethacin :: administration & dosage; Indomethacin :: therapeutic use; Male; Middle Aged; Oxycodone :: administration & dosage; Oxycodone :: therapeutic use; Pain Measurement; Pain, Postoperative :: epidemiology; Pain, Postoperative :: prevention & control; Parasympatholytics :: administration & dosage; Parasympatholytics :: therapeutic use; Support, Non-U.S. Gov't; Thoracotomy :: adverse effects; Time Factors;
Clinical Site Operations, SCIREX Corp., Austin, Texas, USA.
BACKGROUND: The authors conducted two studies to compare the analgesic efficacy and safety of the cyclooxygenase, or COX,-2-specific inhibitor, valdecoxib, with oxycodone/ acetaminophen in patients who have undergone oral surgery. METHODS: In total, 205 eligible subjects in Study A and 201 in Study B were randomized to receive a single oral dose of valdecoxib (20 or 40 milligrams), a combination of oxycodone 10 mg/acetaminophen 1,000 mg or placebo. Eligible subjects experienced moderate-to-severe pain within six hours of surgery during which two or more impacted third molars were extracted. Analgesic efficacy was assessed over 24 hours or until the patient required rescue analgesia. RESULTS: In both studies, subjects receiving either dose of valdecoxib experienced a rapid onset of analgesia and (among those who received valdecoxib 40 mg) a level of pain relief comparable with that of those who received oxycodone/ acetaminophen. Both valdecoxib doses had a significantly longer duration of analgesic effect than did oxycodone/acetaminophen. Pooled safety data demonstrated that each valdecoxib dose had a tolerability profile superior to that of oxycodone/ acetaminophen and similar to that of placebo. CONCLUSIONS: Orally administered valdecoxib is as rapidly acting and effective as oxycodone/acetaminophen, and it has a superior duration of analgesic effect in patients after oral surgery. Valdecoxib has a tolerability profile superior to that of oxycodone/acetaminophen. CLINICAL IMPLICATIONS: The current standard of care for alleviating acute pain after oral surgery has rested largely on conventional nonsteroidal anti-inflammatory drugs or opioid/analgesic combination products. The studies reported here suggest that the COX-2-specific inhibitor valdecoxib offers an efficacious and safe alternative to other analgesics used to treat pain after oral surgery.
Mesh-terms: Acetaminophen :: administration & dosage; Adult; Analgesics, Non-Narcotic :: administration & dosage; Analgesics, Opioid :: administration & dosage; Analysis of Variance; Comparative Study; Consumer Product Safety; Cyclooxygenase Inhibitors :: administration & dosage; Double-Blind Method; Drug Combinations; Female; Human; Isoxazoles :: administration & dosage; Male; Molar, Third :: surgery; Oxycodone :: administration & dosage; Pain, Postoperative :: etiology; Pain, Postoperative :: prevention & control; Sulfonamides :: administration & dosage; Support, Non-U.S. Gov't; Tooth Extraction :: adverse effects; Tooth, Impacted :: surgery;
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.
Six rationales for using combination analgesics are identified, but most combinations are formulated with two rationales in mind: enhancement of analgesia and reduction of adverse effects by combining two analgesics with different mechanisms of action. Acetaminophen and aspirin are the mainstays of oral analgesic combinations. There is substantial evidence that combining an optimal dose of acetaminophen or aspirin with an oral opioid such as codeine, hydrocodone, or oxycodone produces an additive analgesic effect greater than that obtained by doubling the dose of either constituent administered alone. There is also some evidence that the adverse effects produced by such combinations are less than would be produced by an equi-analgesic dose of a single constituent. The physician need not be confined to existing fixed-ratio combinations; he or she may extemporize to the patient's advantage by co-administering acetaminophen, aspirin, or other nonsteroidal anti-inflammatory drugs with available oral opioids and, in select situations, co-administering oral or injectable analgesics with psychoactive drugs.
Mesh-terms: Acetaminophen :: administration & dosage; Acetaminophen :: adverse effects; Analgesics :: administration & dosage; Analgesics :: adverse effects; Aspirin :: administration & dosage; Aspirin :: adverse effects; Caffeine :: administration & dosage; Codeine :: administration & dosage; Drug Interactions; Drug Therapy, Combination; Human; Hydrocodone :: administration & dosage; Narcotics :: administration & dosage; Narcotics :: adverse effects; Oxycodone :: administration & dosage; Phenacetin :: administration & dosage; Primary Health Care; Propoxyphene :: administration & dosage; Tranquilizing Agents :: administration & dosage;
Regional Oncology Hematology Associates, Kissimmee, Florida, USA.
Two separate trials compared controlled-release (CR) oral oxycodone (administered every 12 hours) with immediate-release (IR) oxycodone (4 times a day) to determine whether patients with chronic pain could be titrated to stable pain control as readily with the CR as with the IR formulation. In one study, 48 patients with cancer pain were randomized to open-label titration with either CR or IR oxycodone (maximum dose, 400 mg/day) for a period of up to 21 days. In a study of similar design, 57 patients with low back pain were titrated with either CR or IR oxycodone (maximum dose, 80 mg/day) for a period of up to 10 days. The majority of patients in both studies were converted to oxycodone from other opioid analgesics. Results of both studies showed no difference between CR and IR oxycodone with respect to both the percentage of patients achieving stable pain control, the time to achieve stable pain control, and the degree of pain control achieved. Among cancer patients, 85% achieved stable analgesia, 92% with the CR formulation and 79% with the IR formulation. Among noncancer patients, 91% achieved stable pain control, 87% with the CR formulation and 96% with the IR formulation. The most commonly reported adverse effects in both studies were similar for the two formulations and were those anticipated with opioids: nausea, vomiting, constipation, somnolence, dizziness, and pruritus. Nausea and vomiting were the most frequently cited reasons for treatment discontinuations. These studies suggest that dose titration can be accomplished as readily with oral CR oxycodone as with IR oxycodone in patients with chronic, moderate to severe pain.
Mesh-terms: Adult; Aged; Aged, 80 and over; Analgesics, Opioid :: administration & dosage; Analgesics, Opioid :: adverse effects; Analgesics, Opioid :: therapeutic use; Chronic Disease; Delayed-Action Preparations; Female; Human; Male; Middle Aged; Oxycodone :: administration & dosage; Oxycodone :: adverse effects; Oxycodone :: therapeutic use; Pain :: drug therapy;
Department of Anesthesiology Pain Service, Montefiore Medical Center, Bronx, NY, USA.
PURPOSE: This study compared the clinical efficacy of oxycodone hydrochloride controlled-release (CR) tablets administered every 12 hours with immediate-release (IR) oxycodone tablets administered four times daily in patients with cancer-related pain. PATIENTS AND METHODS: Cancer patients who required therapy for moderate to severe pain were randomized to CR oxycodone every 12 hours (n=81) or IR oxycodone four times daily (n=83) for 5 days in a multicenter, double-blind study. Pain intensity was assessed four times daily (categorical scale of none, slight, moderate, and severe); acceptability of therapy was assessed twice daily (categorical scale of very poor, poor, fair, good, and excellent). RESULTS: Pain intensity remained slight during the study, with mean oxycodone doses of 114 mg/d (range, 20 to 400 mg/d) for CR and 127 mg/d (range, 40 to 640 mg/d) for IR. Acceptability of therapy was fair to good with both treatments. While standard conversion ratios provided an acceptable dose for many patients, a protocol amendment that allowed initial titration and use of rescue medication reduced the discontinuation rate for lack of acceptable pain control (from 34% to 4% with CR and from 31% to 19% with IR before and after amendment, respectively) without increasing the discontinuation rate for adverse events (from 8% to 7% with CR and from 13% to 11% with IR). Fewer adverse events were reported with CR (109) than with IR (186) oxycodone (P=.006). CONCLUSION: CR oxycodone every 12 hours was as effective as IR oxycodone four times daily in managing moderate to severe cancer-related pain and was associated with fewer reports of adverse events.
Mesh-terms: Analgesics, Opioid :: administration & dosage; Analgesics, Opioid :: adverse effects; Analgesics, Opioid :: pharmacokinetics; Analgesics, Opioid :: therapeutic use; Delayed-Action Preparations; Double-Blind Method; Female; Human; Male; Middle Aged; Neoplasms :: complications; Neoplasms :: metabolism; Oxycodone :: administration & dosage; Oxycodone :: adverse effects; Oxycodone :: pharmacokinetics; Oxycodone :: therapeutic use; Pain :: drug therapy; Pain :: metabolism; Pain Measurement; Patient Acceptance of Health Care; Support, Non-U.S. Gov't;
