CMAJ 2006 May 23; 174(11): 1589-94 (Read article online)

Furlan AD, Sandoval JA, Mailis-Gagnon A, Tunks E

BACKGROUND: Chronic noncancer pain (CNCP) is a major health problem, for which opioids provide one treatment option. However, evidence is needed about side effects, efficacy, and risk of misuse or addiction. METHODS: This meta-analysis was carried out with these objectives: to compare the efficacy of opioids for CNCP with other drugs and placebo; to identify types of CNCP that respond better to opioids; and to determine the most common side effects of opioids. We searched MEDLINE, EMBASE, CENTRAL (up to May 2005) and reference lists for randomized controlled trials of any opioid administered by oral or transdermal routes or rectal suppositories for CNCP (defined as pain for longer than 6 mo). Extracted outcomes included pain, function or side effects. Methodological quality was assessed with the Jadad instrument; analyses were conducted with Revman 4.2.7. RESULTS: Included were 41 randomized trials involving 6019 patients: 80% of the patients had nociceptive pain (osteoarthritis, rheumatoid arthritis or back pain); 12%, neuropathic pain (postherpetic neuralgia, diabetic neuropathy or phantom limb pain); 7%, fibromyalgia; and 1%, mixed pain. The methodological quality of 87% of the studies was high. The opioids studied were classified as weak (tramadol, propoxyphene, codeine) or strong (morphine, oxycodone). Average duration of treatment was 5 (range 1-16) weeks. Dropout rates averaged 33% in the opioid groups and 38% in the placebo groups. Opioids were more effective than placebo for both pain and functional outcomes in patients with nociceptive or neuropathic pain or fibromyalgia. Strong, but not weak, opioids were significantly superior to naproxen and nortriptyline, and only for pain relief. Among the side effects of opioids, only constipation and nausea were clinically and statistically significant. INTERPRETATION: Weak and strong opioids outperformed placebo for pain and function in all types of CNCP. Other drugs produced better functional outcomes than opioids, whereas for pain relief they were outperformed only by strong opioids. Despite the relative shortness of the trials, more than one-third of the participants abandoned treatment.

J Pain Symptom Manage 2006 May; 31(5): 457-464 (Read article online)

Llanes LR, Fassbender K, Baracos VE, Watanabe S

Drugs are indispensable for the management of symptoms in palliative care patients, and account for a significant proportion of expenditures on a Tertiary Palliative Care Unit (TPCU). Drug expenditures for Edmonton's TPCU increased by 40% in 2002 compared to 2001. Fifty-five percent of the increase was attributable to injectable fentanyl, oral and injectable ondansetron, and total parenteral nutrition (TPN). As there was no increase in the unit cost of these drugs between 2001 and 2002, the increased expenditures reflected increased utilization. The hypothesis of this study was that the increased utilization of these drugs reflected appropriate prescribing. The objective was to compare the indications for prescribing these drugs in 2002 against evidence- and consensus-based criteria. Patients who received these drugs while admitted to the TPCU from January 1 to December 31, 2002 were identified through the pharmacy database. Evidence- and consensus-based criteria for drug utilization were developed. Prescribing indications were retrospectively compared against the criteria. Drug prescriptions were categorized as follows: (1) meeting criteria, (2) not meeting criteria, or (3) uncertain. The drugs under study were prescribed during 48 out of 234 admissions to the TPCU in 2002. Prescriptions for fentanyl met criteria in 26 of 29 cases. Indications were unsuccessful therapy with morphine, hydromorphone, and oxycodone (20), requirement for rapid titration from fentanyl patch (5), renal failure (2), and sublingual administration for breakthrough pain (1). Prescriptions for ondansetron met criteria in 19 of 21 cases. Indications were nausea refractory to metoclopramide and dexamethasone (13), and nausea related to radiotherapy or chemotherapy (6). Prescriptions for TPN met criteria for initiation in only one of five cases. However, in all cases, TPN had been started prior to admission. In cases where death was considered imminent, TPN was continued pending consultation with the patient and family regarding discontinuation. These data indicate that the increased prescribing of fentanyl and ondansetron on the TPCU satisfied evidence- and consensus-based criteria in most cases, apparently justifying the associated increase in drug expenditures. This type of analysis may be useful whenever increased drug utilization requires review. A cost effectiveness analysis would be the next step in evaluating the costs vs. the benefits. The issue of discontinuing TPN in palliative care patients requires further investigation.

Anesth Analg 2006 Jun; 102(6): 1768-74 (Read article online)

Lemberg K, Kontinen VK, Viljakka K, Kylänlahti I, Yli-Kauhaluoma J, Kalso E

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.

Electrophoresis 2006 May 22; (Read article online)

Baldacci A, Thormann W

CE-ESI multistage IT-MS (CE-MS(n), n

J Pain Palliat Care Pharmacother 2006; 20(2): 5-13 (Read article online)

Passik SD, Hays L, Eisner N, Kirsh KL

There has been intense interest in the problem of prescription drug abuse on the parts of health professionals, law enforcement, the media, and the general public. Clinicians not only need to know how to assess risk but also what drugs are being diverted most in their region. We conducted a prospective survey of prescription drug abusers entering a treatment facility in central Kentucky. Participants (n = 109) were enrolled and completed a structured clinical interview and prescription drug abuse survey. The prescription drug abusers assessed in the study had a mean age of 30.95 years (SD = 10.21), were comprised of 75 men (69%) and 34 women (31%), and were mostly Caucasian (98%). The majority (84%) stated that they had legitimately been given a prescription for opioids for pain at some point from a physician and 61% reported chronic pain concerns. The most commonly abused drugs were hydrocodone-containing formulations (78%) and oxycodone-containing products (69%), while products containing methadone (23%) or fentanyl (7%) were abused much less frequently. Most respondents (91%) stated that they had purchased prescription opioids from a street dealer at least once and the majority (80%) had altered the delivery system of the prescription drug by chewing, snorting, or using IV administration. Implications for pain management are discussed, focusing on the need for clinicians treating chronic pain to more thoroughly assess patients for their risk of abuse and addiction before starting an opioid regimen.

Health Serv Res 2006 Jun; 41(3 Pt 1): 837-55 (Read article online)

Curtis LH, Stoddard J, Radeva JI, Hutchison S, Dans PE, Wright A, Woosley RL, Schulman KA

Objective. To measure geographic variation in opioid use in a large, commercially insured, outpatient population in the United States. Data Sources. Outpatient prescription drug claims database of a national pharmaceutical benefit manager for 7,873,337 subjects with at least one prescription drug claim in 2000. Study Design. We measured the period prevalence of claims for opioid analgesics and controlled-release oxycodone at the state level. We measured geographic variation using the weighted coefficient of variation and systematic component of variation. In county-level multivariable regression, we explored associations between potential explanatory variables and claims for opioid analgesics and controlled-release oxycodone. Principal Findings. A total of 567,778 (64.2 per 1,000 total claims) were for oral opioid analgesics. Claim rates by state ranged from <20 to >100 claims per 1,000 total claims. States with long-standing prescription monitoring programs had among the lowest rates. In the county-level data, presence of a statewide prescription monitoring program and proportions of the population aged 15-24 and 65 years and older were independently and negatively associated with claim rates for all opioid analgesics. Surgeons per 1,000, proportion of the population reporting illicit drug use, and proportion who were female were independently and positively associated with claim rates for all opioid analgesics. Only the proportion of the population aged 25-34 and number of surgeons per 1,000 were independently and positively associated with claim rates for oxycodone. Conclusions. Claim rates for opioid analgesics vary significantly by state. Presence of a statewide prescription monitoring program is associated with lower claim rates at the county level. Future research should use individual-level data to assess whether these findings reflect a reduction in abuse and diversion or suboptimal treatment of pain.

Br J Cancer 2006 May 16; (Read article online)

Bell RF, Wisløff T, Eccleston C, Kalso E

This qualitative systematic review of the clinical methodology used in randomised, controlled trials of oral opioids (morphine, hydromorphone, oxycodone) for cancer pain underlines the difficulties of good pain research in palliative care. The current literature lacks placebo-controlled superiority trials. Recommendations for future research are discussed.British Journal of Cancer advance online publication, 16 May 2006; doi:10.1038/sj.bjc.6603162 www.bjcancer.com.

Gan To Kagaku Ryoho 2006 May; 33(5): 611-5 (Read article online)

Koshikawa T, Shimoyama N

Multi-disciplinary team work among visiting doctors, nurses, care managers and pharmacists located close to the patient's home is essential for smooth transition of a palliative care patient from hospital care to palliative home care and should be set up prior to the patient's discharge from the hospital. Palliative home care physicians should have knowledge of the fundamental support by the government to spare excessive cost to the patients. As for cancer pain management, opioid-centered analgesic therapies have lead to better quality home care for patients. In Japan, although oxycodone SRs and fentanyl patches are available besides morphine, there is no rescue opioid other than morphine. On the other hand,some cancer pain refractory to opioids such as neuropathic cancer pain should be carefully treated by adjuvant analgesics in conjunction with non-pharmacological treatments.

Horm Behav 2006 May 5; (Read article online)

Hibel LC, Granger DA, Kivlighan KT, Blair C,

The purpose of the present study was to describe associations between the use of common over-the-counter (OTC) and prescription medications with individual differences in salivary cortisol in infants and their mothers. Participants were 1020 mothers and 852 infants (52.5% boys; ages 5.03-13.44 months) from economically disadvantaged and ethnically diverse families (38.4% African American) who donated saliva samples before, 20 and 40 min after infants participated in a series of challenging tasks. Samples (N=5616) were later assayed for cortisol. Medication information was content analyzed separately for infants (e.g., teething gels, nonsteroidal anti-inflammatory drugs, acetaminophen, decongestants) and mothers (e.g., narcotics, antidepressants, antipsychotics, contraceptives, glucocorticoids). A large percentage of infants (44%) and the majority of mothers (57.5%) had used at least one medication (range 0-4) in the previous 48 h. Most frequent were acetaminophen (e.g., Tylenol(R)) and cold medications (e.g., decongestants) for infants and contraceptives and acetaminophen for mothers. Compared to infants not taking any medications, cortisol reactivity to the challenge tasks was less pronounced for infants taking acetaminophen. Cortisol levels were higher for mothers taking oral or transdermal contraceptives and acetylsalicylic acid (e.g., Aspirin(R)) but lower for mothers taking pure agonist opioids (e.g., Oxycontin(R)) compared to mothers not taking any medications. These medication-related differences remained significant after controlling for sampling time, fever, maternal anxiety and depression, infant temperament, ethnicity, SES, and health status. Recommendations are provided to steer investigators clear of these potential sources of unsystematic error variance in salivary cortisol.

Clin Pharmacol Ther 2006 May; 79(5): 461-79 (Read article online)

Lalovic B, Kharasch E, Hoffer C, Risler L, Liu-Chen LY, Shen DD

BACKGROUND: In vitro experiments suggest that circulating metabolites of oxycodone are opioid receptor agonists. Clinical and animal studies to date have failed to demonstrate a significant contribution of the O-demethylated metabolite oxymorphone toward the clinical effects of the parent drug, but the role of other putative circulating active metabolites in oxycodone pharmacodynamics remains to be examined. METHODS: Pharmacokinetics and pharmacodynamics of oxycodone were investigated in healthy human volunteers; measurements included the time course of plasma concentrations and urinary excretion of metabolites derived from N-demethylation, O-demethylation, and 6-keto-reduction, along with the time course of miosis and subjective opioid side effects. The contribution of circulating metabolites to oxycodone pharmacodynamics was analyzed by pharmacokinetic-pharmacodynamic modeling. The human study was complemented by in vitro measurements of opioid receptor binding and activation studies, as well as in vivo studies of the brain distribution of oxycodone and its metabolites in rats. RESULTS: Urinary metabolites derived from cytochrome P450 (CYP) 3A-mediated N-demethylation of oxycodone (noroxycodone, noroxymorphone, and alpha- and beta-noroxycodol) accounted for 45% +/- 21% of the dose, whereas CYP2D6-mediated O-demethylation (oxymorphone and alpha- and beta-oxymorphol) and 6-keto-reduction (alpha- and beta-oxycodol) accounted for 11% +/- 6% and 8% +/- 6% of the dose, respectively. Noroxycodone and noroxymorphone were the major metabolites in circulation with elimination half-lives longer than that of oxycodone, but their uptake into the rat brain was significantly lower compared with that of the parent drug. Pharmacokinetic-pharmacodynamic modeling indicated that the time course of pupil constriction is fully explained by the plasma concentration of the parent drug, oxycodone, alone. The metabolites do not contribute to the central effects, either because of their low potency or low abundance in circulation or as a result of their poor uptake into the brain. CONCLUSIONS: CYP3A-mediated N-demethylation is the principal metabolic pathway of oxycodone in humans. The central opioid effects of oxycodone are governed by the parent drug, with a negligible contribution from its circulating oxidative and reductive metabolites.

Arch Intern Med 2006 Apr 24; 166(8): 837-43 (Read article online)

Reid CM, Martin RM, Sterne JA, Davies AN, Hanks GW

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.

Drug Alcohol Depend 2006 Jun; 83 Suppl 1: S40-7 (Read article online)

Fudala PJ, Johnson RE

Non-medical abuse of prescription opioid medications is not a new phenomenon, but such use has been increasing in recent years. Various methods have been used and continue to be developed in an effort to limit diversion and abuse of opioid medications. A number of these methods will be described for opioid analgesic and addiction treatment formulations using relevant historical examples (e.g. propoxyphene, pentazocine, buprenorphine) as well as examples of formulations currently being considered or under development (e.g. oxycodone plus naltrexone, sustained-release buprenorphine). The focus, though not exclusively, will be on those formulations that represent a combination of an opioid agonist with an antagonist. These methods must take into consideration the pharmacokinetic profile of the agonist and antagonist, the expected primary route of abuse of the medication and the medication combination, the dose of medication that is likely to be abused, the availability of alternative drugs of abuse, and the population of potential abusers that is being targeted with the revised formulation.

J Anal Toxicol 2006 Jan-Feb; 30(1): 1-5 (Read article online)

Cone EJ, Heit HA, Caplan YH, Gourlay D

Minor metabolic pathways in human subjects have been shown to exist for the conversion of codeine to hydrocodone but have not been reported for the metabolic conversion of morphine to hydromorphone. In this study, urine specimens were collected in an out-patient setting from 13 pain patients who were chronically treated with morphine and other opioids (methadone, oxycodone, and fentanyl). The chronic pain patients were chosen for study because they were treated with high-dose morphine and had no personal or family history of addiction. Results of the initial evaluation and follow up of these patients with random urine tests did not indicate opioid misuse. The specimens were analyzed by GC-MS for the presence of hydromorphone. The reporting limit for hydromorphone was 100 ng/mL. Ten of the 13 morphine-treated patients excreted hydromorphone in minor amounts ranging 120 to 1400 ng/mL. Concurrent morphine concentrations were exceedingly high in these 10 patients and frequently exceeded the upper limit of linearity (> 10,000 ng/mL) of the assay. The ratio of hydromorphone to morphine ranged from 0.015 to 0.024. Morphine concentrations in the three patients in which hydromorphone was not detected tended to be lower than those observed in other patients. For comparison, one additional patient was included in the study, who was prescribed both morphine and hydromorphone. Concentrations of hydromorphone in this patient were in the range of 3400-13,000 ng/mL, while concurrent morphine concentrations were in the range of 3200-6600 ng/mL. These data are highly suggestive that hydromorphone can be produced as a minor metabolite of morphine in humans. Although additional studies in more restricted settings are needed, it is recommended that interpretation of low urinary concentrations of hydromorphone in combination with high concentrations of morphine in morphine-treated pain patients should not be considered as conclusive evidence of hydromorphone misuse.

Anesth Analg 2006 Apr; 102(4): 1234-9 (Read article online)

Salinas FV, Liu SS, Mulroy MF

Total knee arthroplasty (TKA) may result in severe pain, and single-injection femoral nerve blocks (SFNB) have been demonstrated to have a limited duration of analgesia. Continuous femoral nerve blocks (CFNB) can prolong the analgesic duration of SFNB. We prospectively randomized 36 patients undergoing TKA to CFNB versus SFNB and evaluated the effect on hospital length of stay (LOS) as the primary outcome within a standardized clinical pathway. Secondary outcomes included visual analog scale (VAS) pain scores, opioid consumption, and long-term functional recovery at 12 wk. Mean VAS resting scores were significantly lower among patients who received CFNB versus SFNB: first day (1.7 vs 3.3 [P = 0.002]) and second day (0.9 vs 3.2 [P < 0.0001]) after surgery. Mean maximal VAS scores during physical therapy were significantly lower among patients who received CFNB versus SFNB: first day (4.7 vs 6.3 [P = 0.01]) and second day (3.9 vs 6.1 [P = 0.0005]) after surgery. Mean oxycodone consumption was significantly lower among patients who received CFNB versus SFNB: 15 mg versus 40 mg (P = or < 0.0001) on the first day after surgery; 20 mg versus 43 mg (P = 0.0004) on the second day after surgery. There was no difference in hospital LOS (3.8 vs 3.9 days) or long-term functional recovery (117 degrees versus 113 degrees knee flexion at 12 wk) between the two groups. The lack of effect provided by increased duration of analgesia (from CFNB) after TKA may now have minimal impact on hospital LOS and long-term functional recovery in the contemporary healthcare environment within the United States.

J Anal Toxicol 2006 Mar; 30(2): 106-11 (Read article online)

Haller CA, Stone J, Burke V, Branch J, Chen K, Gross S

OxyContin, a controlled-release formulation of oxycodone, is increasingly abused. Monitoring patient compliance by urine drug testing may deter illegal diversion of OxyContin. Two urine immunoassays were evaluated with a 100 ng/mL cutoff for oxycodone. The Microgenics Corporation Oxycodone DRI on the Bayer ADVIA 1650 and a point-of-care (POC) immunoassay, Monitect Oxycodone POC from Branan Medical Corporation, were compared to gas chromatography-mass spectrometry (GC-MS) with a detection limit of 50 ng/mL free oxycodone. Between-day precision for DRI yielded coefficients of variation from 3.9% to 7.0% at 75 and 125 ng/mL. Fifty-two positive and 52 negative urines were tested. The DRI had a 100% agreement with GC-MS. Two positive specimens had free oxycodone < 50 ng/mL, but oxycodone metabolites, oxymorphone and oxycodone glucuronide > 100 ng/mL, were identified by GC-MS analysis. The POC assay had two false positives and 15 indeterminate (+/-) results. Codeine or hydrocodone was present in all but one of these samples. There was no interference with DRI from morphine, codeine, hydrocodone, hydromorphone, dihydrocodeine, or 6-monoacetyl morphine. Four-hundred and ninety urine samples were subsequently tested with DRI to estimate the oxycodone-positive rate at our hospital, and 47 (9.4%) were positive. The confirmation rate with GC-MS for free oxycodone, not including metabolites, was 93%. The Microgenics DRI offers good performance for oxycodone urine testing and is a better choice for the clinical laboratory than the POC assay. Confirmation of screened positive samples requires a method that can detect total oxycodone and oxymorphone.

J Mass Spectrom 2006 Mar 15; (Read article online)

Musshoff F, Trafkowski J, Kuepper U, Madea B

A fully validated liquid chromatographic procedure coupled with electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) is presented for quantitative determination of the opioids buprenorphine, codeine, fentanyl, hydromorphone, methadone, morphine, oxycodone, oxymorphone, piritramide, tilidine, and tramadol together with their metabolites bisnortilidine, morphine-glucuronides, norfentanyl, and nortilidine in blood plasma after an automatically performed solid-phase extraction (SPE). Separation was achieved in 35 min on a Phenomenex C12 MAX-RP column (4 microm, 150 x 2 mm) using a gradient of ammonium formiate buffer (pH 3.5) and acetonitrile. The validation data were within the required limits. The assay was successfully applied to authentic plasma samples, allowing confirmation of the diagnosis of overdose situations as well as monitoring of patients' compliance, especially in patients under palliative care. Copyright (c) 2006 John Wiley & Sons, Ltd.

Am J Manag Care 2006 Apr; 12(4): 205-14 (Read article online)

Marshall DA, Strauss ME, Pericak D, Buitendyk M, Codding C, Torrance GW

OBJECTIVE: To examine, in routine practice, the effectiveness and cost-effectiveness of oxycodone (OxyContin) compared with standard therapy for osteoarthritis pain. STUDY DESIGN: Open-label active-controlled randomized naturalistic 4-month study of oxycodone vs a combination of oxycodone-acetaminophen (Percocet). METHODS: Outcomes and health resource utilization data were collected by telephone interview. Effectiveness was measured among 485 patients as the proportion having at least 20% improvement from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index pain score. Quality-adjusted life-years (QALYs) were calculated from the Health Utilities Index 3 score. Cost-effectiveness was measured as cost per patient improved and the QALYs gained, using generic oxycodone-acetaminophen in the base case for the healthcare and societal perspectives. Uncertainty was evaluated using multiple 1-way sensitivity analyses and cost-effectiveness acceptability curves. RESULTS: Improvement occurred in 62.2% of patients with oxycodone and in 45.9% of patients with oxycodone-acetaminophen (P < .001). After adjustment for baseline differences, 0.0105 QALYs were gained with oxycodone compared with oxycodone-acetaminophen (P = .17). The mean societal costs per patient during 4 months were 7379 US dollars and 7528 US dollars for oxycodone and oxycodone-acetaminophen, respectively (P = .33). Oxycodone was more effective and less costly than oxycodone-acetaminophen based on the societal perspective (including costs associated with time lost). Based on the healthcare perspective (excluding costs associated with time lost), the cost-effectiveness of oxycodone was 4883 US dollars per patient improved and 75,810 US dollars per QALY gained. The base-case results were robust. CONCLUSIONS: From the societal perspective, oxycodone was more effective and less costly than oxycodone-acetaminophen. From the healthcare perspective, oxycodone (compared with generic oxycodone-acetaminophen) fell within the acceptable range of cost-effectiveness between 50,000 US dollars and 100,000 US dollars per QALY gained.

J Clin Pharmacol 2006 Apr; 46(4): 433-42 (Read article online)

El-Tahtawy A, Kokki H, Reidenberg BE

Young children are often undertreated for pain. One barrier to effective pain treatment is understanding the pharmacokinetic behavior of analgesics in this age group. Oxycodone is a commonly prescribed opioid for severe pain, yet little is known about its pharmacokinetics in young children. This article used population pharmacokinetic modeling to synthesize pharmacokinetic data from several studies into a model. A single population model that described the observed pharmacokinetics was developed. The combined data were best described with a 2-compartment linear model with different first-order absorption rates depending on route of administration. Weight was found to significantly influence both clearance (CL) and volume of distribution (Vd). The following model adequately describes the population pharmacokinetic profile of oxycodone where absolute bioavailability (F) is estimated for each administration route: CL/F=55x(body weight/70)0.87; V/F=86x(body weight/70)1.16. The interindividual coefficients of variation in CL and Vd were 20.2 and 19.7%, respectively. This finding confirms that the allometric scaling using the above model explained most of the variability in exposure observed among children. This model confirms using a weight-based dose for oxycodone without adjustment for age between 6 months and 7 years and is valuable for evaluating dosing schedules and dosing routes.

Consult Pharm 2004 Feb; 19(2): 118-32 (Read article online)

Ackerman SJ, Knight T, Schein J, Carter C, Staats P

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.

Gan To Kagaku Ryoho 2006 Apr; 33(4): 529-32 (Read article online)

Shinjo T, Okada M

Dyspnea is a common symptom in patients with advanced cancer. Systemic morphine administration has been reported as an effective pharmacological treatment to control dyspnea. However, there have been few reports on similar effects of alternative opioids except for morphine. To evaluate the effect of controlled-release oxycodone on the relief of dyspnea,we investigated three cases with opioid substitution from subcutaneous morphine to oral oxycodone. In all cases,both opioids provided equivalent effects for the palliation of cancer dyspnea with no significant adverse effects. Future studies in the appropriate clinical designs will be needed to confirm our findings.