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Sample records for oxycodone controlled release

  1. Oxycodone controlled release in cancer pain management.

    PubMed

    Biancofiore, Giuseppe

    2006-09-01

    Oral opioids are the treatment of choice for chronic cancer pain. Morphine is the strong opioid of choice for the treatment of moderate to severe cancer pain according to guidelines from the World Health Organization (WHO). This recommendation by the WHO was derived from availability, familiarity to clinicians, established effectiveness, simplicity of administration, and relative inexpensive cost. It was not based on proven therapeutic superiority over other options. Patients who experience inadequate pain relief or intolerable side effects with one opioid may often be successfully treated with another agent or with the same agent administered by a different route. Opioid rotation, or switching to an alternative opioid, helps some patients achieve better pain control with fewer associated adverse effects. Oxycodone is a mu-opioid receptor specific ligand, with clear agonist properties. It is an active potent opioid, which is in part a kappa-receptor agonist. Like morphine and other pure agonists, there is no known ceiling to the analgesic effects of oxycodone. The active metabolites of oxycodone (eg, oxymorphone) could be important in oxycodone-mediated analgesia. The main pharmacokinetic difference between oxycodone and morphine is in oral bioavailability. The bioavailability of oxycodone is >60% and the bioavailability of morphine is 20%. Controlled-release oxycodone is absorbed in a bi-exponential fashion. There is a rapid phase with a mean half-life of 37 min, accounting for 38% of the dose, and a slow phase with a half-life of 6.2 h, which accounts for the residual 62%. Oxycodone elimination is impaired by renal failure because there are both an increased volume of distribution and reduced clearance. A lot of studies prove that the efficacy of controlled-release oxycodone in cancer-pain control is at least the same as morphine, immediate-release oxycodone and hydromorphone. Its toxicity profile seems better than that of morphine. There are actually several

  2. Normal-release and controlled-release oxycodone: pharmacokinetics, pharmacodynamics, and controversy.

    PubMed

    Davis, Mellar P; Varga, James; Dickerson, Duke; Walsh, Declan; LeGrand, Susan B; Lagman, Ruth

    2003-02-01

    Oxycodone has become one of the most popular opioids in the United States. It is superior to morphine in oral absorption and bioavailability, and similar in terms of protein binding and lipophilicity. Gender more than age influences oxycodone elimination. Unlike morphine, oxycodone is metabolized by the cytochrome isoenzyme CYP2D6, which is severely impaired by liver dysfunction. Controlled-release (CR) oxycodone has become one of the most frequently utilized sustained-release opioids in the United States. Both its analgesic benefits and its side effects are similar to those of CR morphine. CR oxycodone is similar to morphine and other opioids in its abuse potential. Deaths attributable to oxycodone are usually associated with polysubstance abuse in which oxycodone is combined with psychostimulants, other opioids, benzodiazepines or alcohol. Oxycodone's kappa receptor binding has little role in abuse or addiction. The cost of CR oxycodone is prohibitive for most American hospices.

  3. Noninterventional observational study using high-dose controlled-release oxycodone (CR oxycodone) for cancer pain management in outpatient clinics.

    PubMed

    Baek, Sun Kyung; Shin, Hye Won; Choi, Young Jin; Zang, Dae Young; Cho, Do-Yeun; Ryoo, Hun Mo; Baek, Jin Ho; Kim, Sam Yong; Song, Hong-Suk

    2013-12-01

    Efficacy, safety, and quality of life (QoL) for patients receiving larger doses of controlled-release oxycodone (CR oxycodone) in outpatient clinics are evaluated. The use of high-dose CR oxycodone and adjuvant drugs for pain management, pain intensity, parameters associated with quality of life, and adverse effects in cancer patients treated with high-dose CR oxycodone (≥80 mg/day) was prospectively observed for 8 weeks. Data from 486 cancer patients receiving high-dose CR oxycodone were collected from 44 hospitals during the period from February 2009 to March 2010. Three hundred eighteen of the total 486 patients treated with high-dose CR oxycodone were followed up for 8 weeks. Pain intensity significantly improved from a mean numeric rating scale (NRS) 5.49 to NRS 4.33 (P < 0.0001). Dosage of CR oxycodone increased from a mean of 130.0 to a mean of 174.9 (P < 0.0001). QoL including activity, walking, and sleeping significantly improved after 8 weeks. At baseline, 138 complained of adverse effects, of which constipation (30.2%) was the most common followed by dry mouth (8.8%) and dizziness (8.2%). After 8 weeks, 128 patients complained of adverse effects such as constipation (27.0%), nausea (5.7%), dry mouth (5.7%), and dizziness (5.0%). After 8 weeks of high-dose CR oxycodone, adverse effects did not increase. This study suggests that over an 8-week period, the use of high-dose CR oxycodone for cancer pain management is efficient, safe, and tolerable in outpatient clinics. Wiley Periodicals, Inc.

  4. Effects of Aprepitant on the Pharmacokinetics of Controlled-Release Oral Oxycodone in Cancer Patients

    PubMed Central

    Fujiwara, Yutaka; Toyoda, Masanori; Chayahara, Naoko; Kiyota, Naomi; Shimada, Takanobu; Imamura, Yoshinori; Mukohara, Toru; Minami, Hironobu

    2014-01-01

    Purpose Oxycodone is a µ-opioid receptor agonist widely used in the treatment of cancer pain. The predominant metabolic pathway of oxycodone is CYP3A4-mediated N-demethylation to noroxycodone, while a minor proportion undergoes 3-O-demethylation to oxymorphone by CYP2D6. The aim of this study was to investigate the effects of the mild CYP3A4 inhibitor aprepitant on the pharmacokinetics of orally administered controlled-release (CR) oxycodone. Method This study design was an open-label, single-sequence with two phases in cancer patients with pain who continued to be administered orally with multiple doses of CR oxycodone every 8 or 12 hours. Plasma concentration of oxycodone and its metabolites were measured up to 8 hours after administration as follows: on day 1, CR oxycodone was administered alone; on day 2, CR oxycodone was administered with aprepitant (125 mg, at the same time of oxycodone dosing in the morning). The steady-state trough concentrations (Css) were measured from day 1 to day 3. Results Aprepitant increased the area under the plasma concentration-time curve (AUC0–8) of oxycodone by 25% (p<0.001) and of oxymorphone by 34% (p<0.001), as well as decreased the AUC0–8 of noroxycodone by 14% (p<0.001). Moreover, aprepitant increased Css of oxycodone by 57% (p = 0.001) and of oxymorphone by 36% (p<0.001) and decreased Css of noroxycodone by 24% (p = 0.02) at day 3 compared to day 1. Conclusions The clinical use of aprepitant in patients receiving multiple doses of CR oxycodone for cancer pain significantly altered plasma concentration levels, but would not appear to need modification of the CR oxycodone dose. Trial Registration UMIN.ac.jp UMIN000003580. PMID:25121773

  5. Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets.

    PubMed

    Kim, Ju-Young; Lee, Sung-Hoon; Park, Chun-Woong; Rhee, Yun-Seok; Kim, Dong-Wook; Park, Junsang; Lee, Moonseok; Seo, Jeong-Woong; Park, Eun-Seok

    2015-01-01

    The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day]) or once-a-day CR tablets (20 mg) were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone.

  6. Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

    PubMed Central

    Kim, Ju-Young; Lee, Sung-Hoon; Park, Chun-Woong; Rhee, Yun-Seok; Kim, Dong-Wook; Park, Junsang; Lee, Moonseok; Seo, Jeong-Woong; Park, Eun-Seok

    2015-01-01

    The aim of present study was to design oxycodone once-a-day controlled-release (CR) tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC) 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day]) or once-a-day CR tablets (20 mg) were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. PMID:25678774

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

    PubMed

    Havens, Jennifer R; Talbert, Jeffrey C; Walker, Robert; Leedham, Cynthia; Leukefeld, Carl G

    2006-01-01

    Prescription opioid abuse has emerged as a public health problem, particularly in rural America. To examine temporal and geographic trends in rates of controlled-release oxycodone (OxyContin) prescribing for Kentucky Medicaid recipients. 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. 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. 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.

  8. Controlled-release oxycodone and naloxone in the treatment of chronic low back pain: A placebo-controlled, randomized study

    PubMed Central

    Cloutier, C; Taliano, J; O’Mahony, W; Csanadi, M; Cohen, G; Sutton, I; Sinclair, D; Awde, M; Henein, S; Robinson, L; Eisenhoffer, J; Piraino, PS; Harsanyi, Z; Michalko, KJ

    2013-01-01

    BACKGROUND For Canadian regulatory purposes, an analgesic study was required to complement previously completed, pivotal studies on bowel effects and analgesia associated with controlled-release (CR) oxycodone/CR naloxone. OBJECTIVES: To compare the analgesic efficacy and safety of CR oxycodone/CR naloxone versus placebo in patients with chronic low back pain. METHODS: Patients requiring opioid therapy underwent a two- to seven-day opioid washout before being randomly assigned to receive either 10 mg/5 mg CR oxycodone/CR naloxone or placebo every 12 h, titrated weekly according to efficacy and tolerability to 20 mg/10 mg, 30 mg/15 mg or 40 mg/20 mg every 12 h. After four weeks, patients crossed over to the alternative treatment for an additional four weeks. Acetaminophen/codeine (300 mg/30 mg every 4 h to 6 h as needed) was provided as rescue medication. RESULTS: Of the 83 randomized patients, 54 (65%) comprised the per-protocol population. According to per-protocol analysis, CR oxycodone/CR naloxone resulted in significantly lower mean (± SD) pain scores measured on a visual analogue scale (48.6±23.1 mm versus 55.9±25.4 mm; P=0.0296) and five-point ordinal pain intensity scores (2.1±0.8 versus 2.4±0.9; P=0.0415) compared with placebo. After the double-blinded phase, patients and investigators both preferred CR oxycodone/CR naloxone over placebo. These outcomes continued in the 79% of patients who chose to continue receiving CR oxycodone/CR naloxone in a six-month, open-label evaluation. CONCLUSIONS: In patients complying with treatment as per protocol, CR oxycodone/CR naloxone was effective for the management of chronic low back pain of moderate or severe intensity. PMID:23662289

  9. Double-blind, randomized comparison of the analgesic and pharmacokinetic profiles of controlled- and immediate-release oral oxycodone in cancer pain patients.

    PubMed

    Stambaugh, J E; Reder, R F; Stambaugh, M D; Stambaugh, H; Davis, M

    2001-05-01

    Thirty patients with cancer pain completed a double-blind crossover study comparing controlled-release (CR) and immediate-release (IR) oxycodone. In open-label titration (2 to 21 days), these patients were stabilized on IR oxycodone qid. They were then randomized to double-blind treatment with CR oxycodone q12h or IR oxycodone qid for 3 to 7 days followed by crossover at the same daily dose. Mean (+/- SD) pain intensity (0 = none to 10 = severe) decreased from a baseline of 6.0 +/- 2.2 to 2.7 +/- 1.1 after titration with IR oxycodone dosed qid. Pain intensity remained stable throughout double-blind treatment: 2.7 +/- 1.9 with CR oxycodone and 2.8 +/- 1.9 with IR oxycodone. Acceptability of therapy and pain scores correlated with plasma oxycodone concentrations for each interval and were similar for both medications (IR and CR oxycodone). Adverse events were similar for both formulations. Following repeat dosing under double-blind conditions, oral CR oxycodone administered q12h provided analgesia comparable to IR oxycodone given qid.

  10. Patient-reported utilization patterns of fentanyl transdermal system and oxycodone hydrochloride controlled-release among patients with chronic nonmalignant pain.

    PubMed

    Ackerman, Stacey J; Mordin, Margaret; Reblando, Joseph; Xu, Xiao; Schein, Jeff; Vallow, Sue; Brennan, Michael

    2003-01-01

    Although use of long-acting opioid analgesics has increased for chronic nonmalignant pain management, little is known about patient-reported utilization patterns. To assess patient-reported utilization patterns of fentanyl transdermal system and oxycodone hydrochloride (HCl) controlled-release among patients with chronic nonmalignant pain and to compare these patterns to standard dose administration guidelines recommended in the manufacturers. prescribing information (PI). Cross-sectional, observational, multicenter study of English-speaking patients who were seeking chronic nonmalignant pain management from 6 outpatient pain clinics. The inclusion criteria for the study were (1) diagnosis of chronic nonmalignant pain, (2) prescription for and current use of either transdermal fentanyl or oxycodone HCl controlled-release, and (3) duration of use for either transdermal fentanyl or oxycodone HCl controlled-release of at least 6 weeks. Patients completed either an oxycodone HCl controlled-release or transdermal fentanyl utilization questionnaire. A conversion table was used to standardize opioid analgesic doses from transdermal fentanyl or oxycodone HCl controlled-release to daily oral morphine equivalents. The principal outcome measures were the average interval between oxycodone HCl controlled-release administrations, the number of days the current transdermal fentanyl patch would be worn, and the percentage of oxycodone HCl controlled-release and transdermal fentanyl patients whose administration frequency exceeded the standard recommendation in the manufacturer.s PI (every 12 hours for oxycodone HCl controlled-release or every 72 hours for transdermal fentanyl). Other outcome measures included the number of oxycodone HCl controlled-release tablets per administration, the daily dose of long-acting opioid, the duration of adequate pain relief, and the difference in daily oral morphine equivalents between transdermal fentanyl and oxycodone HCl controlled-release

  11. Reformulation of controlled-release oxycodone and pharmacy dispensing patterns near the US–Canada border

    PubMed Central

    Gomes, Tara; Paterson, J Michael; Juurlink, David N; Dhalla, Irfan A; Mamdani, Muhammad M

    2012-01-01

    Background In August 2010, a tamper-resistant formulation of controlled-release oxycodone (OxyContin-OP) was introduced in the United States but not in Canada. Our objective was to determine whether introduction of OxyContin-OP in the United States influenced prescription volumes for the original controlled-release oxycodone formulation (OxyContin) at Canadian pharmacies near the international border. Methods We conducted a population-based, serial, cross-sectional study of prescriptions dispensed from pharmacies in the 3 cities with the highest volume of US–Canada border crossings in Ontario: Niagara Falls, Windsor and Sarnia. We analyzed data on all outpatient prescriptions for OxyContin dispensed by Canadian pharmacies near each border crossing between 2010 Apr. 1 and 2012 Feb. 29. We calculated and compared monthly prescription rates, adjusted per 1000 population and stratified by tablet strength. Results The number of tablets dispensed near 4 border crossings in the 3 Canadian cities remained stable over the study period. However, the rate of dispensing at pharmacies near the Detroit–Windsor Tunnel increased roughly 4-fold between August 2010 and February 2011, from 505 to 1969 tablets per 1000 population. By April 2011, following warnings to prescribers and pharmacies regarding drug-seeking behaviour, the dispensing rate declined to 1683 tablets per 1000 population in this area. By November 2011, the rate had returned to levels observed in early 2010. Our analyses suggest that 242 075 excess OxyContin tablets were dispensed near the Detroit–Windsor Tunnel between August 2010 and October 2011. Conclusions Prescribing of the original formulation of controlled-release oxycodone rose substantially near a major international border crossing following the introduction of a tamper-resistant formulation in the United States. It is possible that the restriction of this finding to the area surrounding the Detroit–Windsor Tunnel reflects specific

  12. Trends in Controlled-Release Oxycodone (Oxycontin[R]) Prescribing among Medicaid Recipients in Kentucky, 1998-2002. Research Note

    ERIC Educational Resources Information Center

    Havens, Jennifer R.; Talbert, Jeffrey C.; Walker, Robert; Leedham, Cynthia; Leukefeld, Carl G.

    2006-01-01

    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…

  13. Trends in Controlled-Release Oxycodone (Oxycontin[R]) Prescribing among Medicaid Recipients in Kentucky, 1998-2002. Research Note

    ERIC Educational Resources Information Center

    Havens, Jennifer R.; Talbert, Jeffrey C.; Walker, Robert; Leedham, Cynthia; Leukefeld, Carl G.

    2006-01-01

    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…

  14. Reduced cognitive and psychomotor impairment with extended-release oxymorphone versus controlled-release oxycodone.

    PubMed

    Schoedel, Kerri A; McMorn, Stephen; Chakraborty, Bijan; Zerbe, Kathleen; Sellers, Edward M

    2010-01-01

    Opioids provide effective pain control, yet have risks including adverse events (AEs) (e.g., constipation, nausea/vomiting, sedation) and cognitive/psychomotor effects. To compare cognitive and psychomotor effects of oxymorphone extended release (OM-ER) versus oxycodone controlled release (OC-CR). Randomized, double-blind, 5-way crossover Single inpatient research unit Nondependent recreational opioid users were administered single intact oral tablets of placebo, OM-ER (15 and 30 mg), and OC-CR (30 and 60 mg), separated by a 7- to 21-day washout. The divided attention (DA) test measured psychomotor impairment (e.g., manual tracking [e.g., percentage over road], target accuracy [e.g., target hits], reaction time [hit latency]). Visual analog scales measured alertness/drowsiness, agitation/relaxation, and dizziness. Sedative, stimulant, and dysphoric effects were measured using the Addiction Research Center Inventory Pentobarbital-Chlorpromazine-Alcohol (PCAG), Benzedrine Group (BG), and Lysergic Acid Diethylamide (LSD) scales, respectively. Comparisons were made between equianalgesic doses (OM-ER 15 mg vs OC-CR 30 mg; OM-ER 30 mg vs OC-CR 60 mg), within active drug doses, and between active drugs and placebo using least squares (LS) mean difference of the peak maximum (Emax) or minimum (Emin) effect using linear mixed model analysis of covariance. Thirty-five participants received all 5 treatments. Peak cognitive and psychomotor impairment (LS mean [SE]) was less with OM-ER than equianalgesic doses of OC-CR for reaction time (Emax hit latency, longer if impaired; 571.2 [13.4] vs 588.1 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg, respectively; 572.4 [13.4] vs 604.3 ms [13.4], P<0.001 for OM-ER 30 mg vs OC-CR 60 mg, respectively); tracking accuracy (Emin percentage over road, lower if impaired; 71.4 [2.4] vs 65.3 [2.4], P=0.007; 69.9 [2.4] vs 59.4 [2.4], P<0.001), and target

  15. Controlled-release oxycodone for the treatment of bortezomib-induced neuropathic pain in patients with multiple myeloma.

    PubMed

    Cartoni, Claudio; Brunetti, Gregorio Antonio; Federico, Vincenzo; Efficace, Fabio; Grammatico, Sara; Tendas, Andrea; Scaramucci, Laura; Cupelli, Luca; D'Elia, Gianna Maria; Truini, Andrea; Niscola, Pasquale; Petrucci, Maria Teresa

    2012-10-01

    Bortezomib, a proteasome inhibitor drug very effective against multiple myeloma, may induce the so-called bortezomib-induced peripheral neuropathy (BIPN), hardly manageable with common analgesic drugs. This study assessed the effectiveness of controlled-release (CR) oral oxycodone in controlling pain and its interference on daily functions of patients with hematologic malignancies affected by BIPN. Forty-six patients (median age, 62 years) affected by myeloma and lymphoma, complaining of BIPN-related pain of moderate-to-severe intensity and unresponsive to previous analgesic treatments, were treated with CR oxycodone. The intensity of continuous and brief pain (BP) along with interference of pain with the common daily dimensions of feeling and function were evaluated by using an 11-point numerical rating scale (NRS); a global patient evaluation of efficacy was also performed. The daily average dose of CR oxycodone administered was 28.46 mg (range, 20-80 mg). The pain intensity decreased from a mean NRS value of 7.6 at baseline to 1.3 on day 14. The frequency of BP was reduced from 61 to 47% of patients and its intensity from 7.4 to 3.1 NRS score. A similar trend to decreasing values was observed for all the daily life functions. Slight- or mild-intensity side effects were observed in 23 patients (51%). At the end of the study, 75% of patients found the treatment effective or very effective. CR oxycodone for relief of BIPN-related pain was effective and well tolerated. The pain control significantly improved also the quality of the daily life functions, which are usually compromised in these suffering patients.

  16. Positive and negative subjective effects of extended-release oxymorphone versus controlled-release oxycodone in recreational opioid users.

    PubMed

    Schoedel, Kerri A; McMorn, Stephen; Chakraborty, Bijan; Potts, Susan L; Zerbe, Kathleen; Sellers, Edward M

    2011-01-01

    To compare the subjective effects of oxymorphone extended release (OM-ER) versus oxycodone controlled release (OC-CR). Randomized, double-blind, crossover study. Inpatient unit. Healthy, nondependent recreational opioid users. Single intact oral tablets that were placebo or contained OM-ER (15 and 30 mg) or OC-CR (30 and 60 mg). Doses were representative of mid-range doses for chronic pain and were calculated using an established opioid conversion table. Visual Analog Scales, Subjective Drug Value (SDV), and Addiction Research Center Inventory (ARCI) measured positive, negative, and balance effects and pupillometry. Equianalgesic comparisons were between OM-ER 15 mg versus OC-CR 30 mg (low doses) and OM-ER 30 mg versus OC-CR 60 mg (high doses). Thirty-five subjects received all five treatments. Positive subjective effects were lower for OM-ER 15 mg versus OC-CR 30 mg and for OM-ER 30 mg versus OC-CR 60 mg in ARCI Morphine Benzedrine Group (< or = 0.01 for both), Good Effects (p < 0.001 for both), Rush (p < 0.001 for both), and High VAS (p < 0.001 for both). Nausea was higher with OC-CR (p < or = 0.02), and Bad Effects were higher for OC-CR 60 mg versus OM-ER 30 mg (p < 0.001). Balance effects were lower for OM-ER versus OC-CR (Drug Liking, p < 0.001; Overall Drug Liking, p < or = 0.006; SDV, p < or = 0.008), except for Take Drug Again (p < 0.001 for OC-CR 30 mg versus OM-ER 15 mg; p = 0.18 for high-dose group). Euphoric mood, nausea, somnolence, vomiting, and dizziness were more common with OC-CR than OM-ER. Single-dose design; use of healthy, recreational opioid users. At equianalgesic doses, single oral intact OM-ER produced lower positive, negative, and balance subjective effects than OC-CR, indicating that analgesic potency may not necessarily be reflected in subjective/objective effects.

  17. Economic study on the impact of side effects in patients taking oxycodone controlled-release for noncancer pain.

    PubMed

    Anastassopoulos, Kathryn P; Chow, Wing; Tapia, Crisanta I; Baik, Rebecca; Ackerman, Stacey J; Biondi, David; Kim, Myoung S

    2012-10-01

    Chronic pain is a prevalent condition in the United States. Musculoskeletal pain, including joint and back pain, is the most common type of chronic pain, and many patients with back pain have a neuropathic component. Pain has direct economic consequences. While oxycodone controlled-release (CR) is one of the most widely used oral long-acting opioids for pain, including pain with a neuropathic component, it is often associated with bothersome side effects, resulting in additional medical resource use (MRU) and costs. To examine the impact on MRU and costs to payers of side effects in patients taking oxycodone CR alone or in combination with other pain medications for noncancer pain (including those with neuropathic pain symptoms). A nationwide convenience sample of adults in the United States, who participated in a survey research panel and reported current use of oxycodone CR for noncancer pain, completed an online survey between November 2, 2010, and December 13, 2010. Respondents were excluded if they reported current use of other extended-release or long-acting opioid prescription medications. The survey consisted of questions on demographics, clinical characteristics, pain characteristics, experience with pain medication, and MRU associated with side effects. Payer costs were calculated based on the MRU reported by the respondents multiplied by Medicare reimbursement rates for hospitalizations and outpatient visits and average wholesale price (AWP) minus 20% for medications. A subgroup of patients who reported neuropathic pain symptoms also was examined. After applying the exclusion criteria, 432 respondents completed the survey. Approximately half of the respondents (n = 219; 50.7%) reported neuropathic pain symptoms. The majority of respondents were Caucasian (88.4%) and female (63.7%) with an average age of 41.8 years (14.89). Respondents most frequently reported low back pain (41.2%), followed by osteoarthritis/rheumatoid arthritis (20.4%), neuropathic pain

  18. Intranasal administration of crushed ALO-02 (extended-release oxycodone with sequestered naltrexone): A randomized, controlled abuse-potential study in nondependent recreational opioid users.

    PubMed

    Setnik, Beatrice; Bramson, Candace; Bass, Almasa; Levy-Cooperman, Naama; Malhotra, Bimal; Matschke, Kyle; Sommerville, Kenneth W; Wolfram, Gernot; Geoffroy, Pierre

    2015-12-01

    ALO-02 is an abuse-deterrent formulation consisting of capsules filled with pellets of extended-release oxycodone surrounding sequestered naltrexone. This randomized, double-blind, placebo-/active-controlled, 4-way crossover study examined the abuse potential of crushed ALO-02 administered intranasally to healthy, nondependent, recreational opioid users. Following drug discrimination and naloxone challenge, eligible participants (n = 32) entered a 4-way crossover treatment phase: crushed single dose of 1 of 2 placebos, ALO-02 30 mg/3.6 mg (oxycodone/naltrexone) or oxycodone immediate-release (IR) 30 mg. Primary end points were Drug Liking and High, measured on visual analog scales (VAS) summarized as maximum effect (Emax ) and effect occurring over 2 hours postdose (AUE0-2  h ). Crushed ALO-02 resulted in significantly lower scores versus oxycodone IR on Drug Liking (Emax , 60.5 vs 92.8; AUE0-2  h , 105.4 vs 160.0, respectively) and High (Emax , 25.2 vs 86.9; AUE0-2  h , 27.1 vs 136.4, respectively; n = 28; P < .0001). Adverse events occurred most frequently with oxycodone IR, followed by ALO-02, then placebo, and were considered mild and consistent with opioid therapy. Crushed ALO-02 administered intranasally to nondependent recreational opioid users resulted in significantly lower scores on Drug Liking/High VAS and other positive subjective measures versus crushed oxycodone IR, suggesting less abuse potential. Demonstration of actual abuse deterrence in the real world requires further research.

  19. Synthetic Geopolymers for Controlled Delivery of Oxycodone: Adjustable and Nanostructured Porosity Enables Tunable and Sustained Drug Release

    PubMed Central

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-01-01

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2∶1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial. PMID:21423616

  20. Synthetic geopolymers for controlled delivery of oxycodone: adjustable and nanostructured porosity enables tunable and sustained drug release.

    PubMed

    Forsgren, Johan; Pedersen, Christian; Strømme, Maria; Engqvist, Håkan

    2011-03-15

    In this article we for the first time present a fully synthetic mesoporous geopolymer drug carrier for controlled release of opioids. Nanoparticulate precursor powders with different Al/Si-ratios were synthesized by a sol-gel route and used in the preparation of different geopolymers, which could be structurally tailored by adjusting the Al/Si-ratio and the curing temperatures. In particular, it was shown that the pore sizes of the geopolymers decreased with increasing Al/Si ratio and that completely mesoporous geopolymers could be produced from precursor particles with the Al/Si ratio 2:1. The mesoporosity was shown to be associated with a sustained and linear in vitro release profile of the opioid oxycodone. A clinically relevant release period of about 12 h was obtained by adjusting the size of the pellets. The easily fabricated and tunable geopolymers presented in this study constitute a novel approach in the development of controlled release formulations, not only for opioids, but whenever the clinical indication is best treated with a constant supply of drugs and when the mechanical stability of the delivery vehicle is crucial.

  1. Abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered crushed oxycodone HCl abuse-deterrent controlled-release tablets in recreational opioid users.

    PubMed

    Harris, Stephen C; Perrino, Peter J; Smith, Ira; Shram, Megan J; Colucci, Salvatore V; Bartlett, Cynthia; Sellers, Edward M

    2014-04-01

    The objective of this study was to evaluate abuse potential, pharmacokinetics, pharmacodynamics, and safety of intranasally administered, crushed reformulated OxyContin® (oxycodone HCl controlled-release) tablets (ORF), relative to crushed original OxyContin® (OC), oxycodone powder (Oxy API), and OC placebo. This randomized, double-blind, positive- and placebo-controlled crossover study enrolled healthy, adult, nonphysically dependent recreational opioid users with recent history of intranasal drug abuse (N = 27). Active treatments contained oxycodone (30 mg). Pharmacokinetics, pharmacodynamics (e.g., Overall Drug Liking [ODL], Take Drug Again [TDA], and High Visual Analog Scales [VAS]; Subjective Drug Value [SDV]; pupillometry; intranasal irritation), and safety (e.g., adverse events, vital signs, laboratory tests) were assessed to 24 hours postdose. Crushed ORF administration yielded reduced oxycodone Cmax and increased Tmax versus crushed OC and Oxy API. Peak effects for pharmacodynamic measures were delayed with ORF (1-2 hours) versus OC and Oxy API (0.5-1 hour). ODL, TDA, High VAS, and SDV Emax values were significantly lower (P ≤ .05) and some intranasal irritation ratings were greater for ORF versus OC and Oxy API. No significant or unexpected safety findings were observed. Compared with OC and Oxy API, intranasally administered ORF was associated with lower and delayed peak plasma concentrations, decreased drug-liking, and decreased intranasal tolerability. This suggests that ORF has a decreased potential for intranasal oxycodone abuse. There were no significant or unexpected safety findings. As is true for all abuse potential studies, epidemiological or other appropriate post-marketing studies are required to assess the impact of the reduction in intranasal oxycodone abuse potential observed in the present study on real-world patterns of ORF misuse, abuse, and diversion.

  2. A phase III randomized controlled study on the efficacy and improved bowel function of prolonged-release (PR) oxycodone-naloxone (up to 160/80 mg daily) vs oxycodone PR.

    PubMed

    Dupoiron, D; Stachowiak, A; Loewenstein, O; Ellery, A; Kremers, W; Bosse, B; Hopp, M

    2017-06-22

    Oxycodone/naloxone (OXN PR) is a prolonged-release formulation containing oxycodone and naloxone in a 2:1 ratio. This study aimed to evaluate the tolerability and efficacy of doses up to OXN160/80 mg PR compared with oxycodone prolonged-release formulation (OxyPR) in a randomised controlled trial. Two hundred and forty-three patients were randomised to treatment with OXN PR (n = 123) or OxyPR (n = 120) during the 5-week double-blind study. Measured were: opioid-induced constipation [bowel function index score (BFI)]; analgesic efficacy (NRS 0-10); daily laxative rescue medication use; rescue medication use, and the number of complete spontaneous bowel movements (CSBMs) per week. A subanalysis was conducted in cancer patients. Greater reductions in mean BFI scores were reported for the OXN PR group compared with OxyPR from Week 1 onwards; at Week 5 the mean change from baseline was -32.5 versus -14.2. Average 24-h pain scores were low and remained stable in the range 3-4 in both treatment groups. Analgesic rescue medication use was similar between the groups. Patients receiving OXN PR used significantly lower mean daily doses of laxative rescue medication than those receiving OxyPR (P = 0.006). The number of CSBM in the OXN PR group approximately doubled compared with a 25% decrease in the OxyPR group. Comparable results to the total study population were reported in the cancer patient subgroup. OXN PR in daily doses of up to 160/80 mg significantly improves bowel function compared with equivalent doses of OxyPR while still providing comparable analgesic efficacy. Effective analgesia can be achieved using oxycodone/naloxone PR up to 160/80 mg daily without compromising bowel function. A similar outcome was reported in cancer and non-cancer patients. © 2017 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.

  3. Prolonged-Release Oxycodone/Naloxone Improves Anal Sphincter Relaxation Compared to Oxycodone Plus Macrogol 3350.

    PubMed

    Poulsen, Jakob Lykke; Brock, Christina; Grønlund, Debbie; Liao, Donghua; Gregersen, Hans; Krogh, Klaus; Drewes, Asbjørn Mohr

    2017-10-06

    Opioid analgesics inhibit anal sphincter function and contribute to opioid-induced bowel dysfunction (OIBD). However, it is unknown whether the inhibition can be reduced by opioid antagonism with prolonged-release (PR) naloxone and how this compares to laxative treatment. To compare the effects of combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350 on anal sphincter function and gastrointestinal symptoms. A randomized, double-blind, crossover trial was conducted in 20 healthy men. Participants were treated for 5 days with combined PR oxycodone/naloxone or PR oxycodone plus macrogol 3350. Resting anal pressure, anal canal distensibility, and relaxation of the internal sphincter to rectal distension were evaluated before treatment (baseline) and on day 5. The Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire, stool frequency, and stool consistency were assessed daily. Both PR oxycodone/naloxone and PR oxycodone plus macrogol treatment decreased sphincter relaxation compared to baseline (- 27.5%; P < 0.001 and - 14.7%; P = 0.01). However, sphincter relaxation was increased after PR naloxone/oxycodone treatment compared to macrogol (difference = + 17.6%; P < 0.001). Resting anal pressure and anal canal distensibility did not differ between treatments. PAC-SYM abdominal symptoms score was lower during PR naloxone compared to macrogol (0.2 vs. 3.2; P = 0.002). The number of bowel movements was lower during PR naloxone versus macrogol (4.2 vs. 5.4; P = 0.035). Relaxation of the internal anal sphincter was significantly better after PR oxycodone/naloxone treatment compared to PR oxycodone plus macrogol 3350. These findings highlight that OIBD may require specific therapy against the complex, pan-intestinal effects of opioids.

  4. Oxycodone

    MedlinePlus

    ... this type of medication for at least one week. Oxycodone is in a class of medications called ... have stopped taking them within the past two weeks: isocarboxazid (Marplan), linezolid (Zyvox), methylene blue, phenelzine (Nardil), ...

  5. Prolonged release oxycodone-naloxone for treatment of severe restless legs syndrome after failure of previous treatment: a double-blind, randomised, placebo-controlled trial with an open-label extension.

    PubMed

    Trenkwalder, Claudia; Beneš, Heike; Grote, Ludger; García-Borreguero, Diego; Högl, Birgit; Hopp, Michael; Bosse, Björn; Oksche, Alexander; Reimer, Karen; Winkelmann, Juliane; Allen, Richard P; Kohnen, Ralf

    2013-12-01

    Opioids are a potential new treatment for severe restless legs syndrome. We investigated the efficacy and safety of a fixed-dose combination of prolonged release oxycodone-naloxone for patients with severe restless legs syndrome inadequately controlled by previous, mainly dopaminergic, treatment. This multicentre study consisted of a 12-week randomised, double-blind, placebo-controlled trial and 40-week open-label extension phase done at 55 sites in Austria, Germany, Spain, and Sweden. Patients had symptoms for at least 6 months and an International RLS Study Group severity rating scale sum score of at least 15; patients with severe chronic obstructive pulmonary disease or a history of sleep apnoea syndrome were excluded. Patients were randomly assigned (1:1) to either study drug or matched placebo with a validated interactive response technology system in block sizes of four. Study drug was oxycodone 5·0 mg, naloxone 2·5 mg, twice per day, which was up-titrated according to investigator's opinion to a maximum of oxycodone 40 mg, naloxone 20 mg, twice per day; in the extension, all patients started on oxycodone 5·0 mg, naloxone 2·5 mg, twice per day, which was up-titrated to a maximum of oxycodone 40 mg, naloxone 20 mg, twice per day. The primary outcome was mean change in severity of symptoms according to the International RLS Study Group severity rating scale sum score at 12 weeks. This study is registered with ClinicalTrials.gov (number NCT01112644) and with EudraCT (number 2009-011107-23). We screened 495 patients, of whom 306 were randomly assigned and 276 included in the primary analysis (132 to prolonged release oxycodone-naloxone vs 144 to placebo). 197 patients participated in the open-label extension. Mean International RLS Study Group rating scale sum score at randomisation was 31·6 (SD 4·5); mean change after 12 weeks was -16·5 (SD 11·3) in the prolonged release oxycodone-naloxone group and -9·4 (SD 10·9) in the placebo group (mean difference

  6. Pain therapy with oxycodone/naloxone prolonged-release combination: case report.

    PubMed

    Błaszczyk, Feliks; Droń, Aleksandra

    2013-01-01

    Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent - morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin(®) (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control.

  7. Randomized, double-blind, placebo-controlled and active-controlled study to assess the relative abuse potential of oxycodone HCl-niacin tablets compared with oxycodone alone in nondependent, recreational opioid users

    PubMed Central

    Webster, Lynn R; Rolleri, Robert L; Pixton, Glenn C; Sommerville, Kenneth W

    2012-01-01

    Background Abuse-deterrent formulations attempt to address public health and societal concerns regarding opioid abuse. Oxycodone HCl-niacin tablets combine oxycodone HCl with niacin and functional inactive excipients to create potential barriers to oral, intranasal, and intravenous abuse. This study compared the relative abuse potential of oral immediate-release oxycodone HCl-niacin with that of oral immediate-release oxycodone HCl and placebo in nondependent, recreational opioid users. Methods Forty-nine participants received oxycodone HCl-niacin 40/240 mg and 80/480 mg, oxycodone 40 mg and 80 mg, and placebo in a randomized, double-blind, placebo-controlled and active-controlled, five-way crossover study. Primary endpoints based on a bipolar 100 mm visual analog scale for drug liking were area under effect curve (AUE0–1h, AUE0–2h, AUE0–3h), peak disliking, and effect at 0.5 hours post-dose (E0.5h). Other endpoints included take drug again assessment, overall drug liking, and pupillometry. Results There were statistically significant differences between oxycodone HCl-niacin and oxycodone HCl doses for all primary endpoints (P < 0.0001, all comparisons), suggesting reduced abuse potential with oxycodone HCl-niacin. Take drug again and overall drug liking showed greater liking of oxycodone alone. Oxycodone HCl-niacin 80/480 mg had consistently lower liking assessments than oxycodone HCl-niacin 40/240 mg, suggesting a dose-response to the aversive effects of niacin. Opioid-related adverse events were similar for equivalent oxycodone doses. The treatment-emergent adverse events most specifically associated with oxycodone HCl-niacin (ie, skin-burning sensation, warmth, and flushing) were consistent with the expected vasocutaneous effects of niacin. No serious adverse events were reported. Conclusion Oxycodone HCl-niacin tablets may, in a dose-dependent manner, decrease the potential for oral abuse of oxycodone without unexpected adverse events or clinically

  8. Relapsing thrombotic microangiopathy and intravenous sustained-release oxycodone

    PubMed Central

    Nataatmadja, Melissa; Divi, Dakshinamurthy

    2016-01-01

    Thrombotic microangiopathy (TMA) associated with injecting sustained-release oxymorphone, an opioid intended for oral use, has previously been reported. We report a case of TMA secondary to intravenous use of sustained-release oxycodone, and the first case to demonstrate relapsing disease due to persistent intravenous opioid use. In cases such as these, TMA is suspected to be due to a polyethylene oxide (PEO) coating found on these drugs, and the disease is likely due to a directly toxic effect of PEO to endothelial cells. We hypothesize that there are unidentified genetic predispositions causing some persons to be susceptible to developing this disease. PMID:27478601

  9. Perspectives on Intravenous Oxycodone for Control of Postoperative Pain.

    PubMed

    Pergolizzi, Joseph V; Seow-Choen, Francis; Wexner, Steven D; Zampogna, Gianpietro; Raffa, Robert B; Taylor, Robert

    2016-09-01

    Intravenous (IV) analgesia has particular advantages in the immediate postoperative period. For example, IV administration results in a faster onset of pain relief and results in more predictable pharmacokinetics than does administration by other routes. It also allows for convenient dosing before or during surgery, permitting the initiation of effective analgesia in the early phase of the postoperative period. In addition, when patients are able to tolerate oral intake, they can be switched from IV to oral dosing based on maintaining the predictable analgesia established by the IV route. IV morphine is widely used for the control of postoperative pain, but there is a trend toward the use of oxycodone. Oxycodone (which may be mediated partly through kappa- as well as mu-opioid receptors) offers several potential advantages. Published studies comparing IV oxycodone to other IV opioids for postsurgical pain report that oxycodone is a safe and effective analgesic. Some studies show that IV oxycodone may be associated with greater pain control, fewer or less severe adverse events, and faster onset of action, although the results are not consistent across all studies. Oxycodone has been reported to be safe in the geriatric and other special populations when adequate clinical adjustments are made. Thus, the clinical reports and oxycodone's pharmacologic profile make intravenous oxycodone a potentially important "new" old drug for postoperative pain control. © 2015 World Institute of Pain.

  10. Pain therapy with oxycodone/naloxone prolonged-release combination: case report

    PubMed Central

    Droń, Aleksandra

    2013-01-01

    Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent – morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin® (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control. PMID:24592131

  11. A randomized, double-blind, active-controlled, double-dummy, parallel-group study to determine the safety and efficacy of oxycodone/naloxone prolonged-release tablets in patients with moderate/severe, chronic cancer pain

    PubMed Central

    Ahmedzai, Sam H; Nauck, Friedemann; Bar-Sela, Gil; Bosse, Björn; Leyendecker, Petra

    2012-01-01

    Objective: An examination of whether oxycodone/naloxone prolonged-release tablets (OXN PR) can improve constipation and maintain analgesia, compared with oxycodone prolonged-release tablets (OxyPR) in patients with moderate/severe cancer pain. Methods: Randomized, double-blind, active-controlled, double-dummy, parallel-group study in which 185 patients were randomized to receive up to 120 mg/day of OXN PR or OxyPR over 4 weeks. Efficacy assessments included Bowel Function Index (BFI), Brief Pain Inventory Short-Form (BPI-SF), laxative and rescue medication use. Quality of life (QoL) and safety assessments were conducted. Results: After 4 weeks, mean BFI score was significantly lower with OXN PR; mean total laxative intake was 20% lower with OXN PR. Mean BPI-SF scores were similar for both treatments and the average rate of analgesic rescue medication use was low and comparable. QoL assessments were stable and comparable with greater improvements in constipation-specific QoL assessments with OXN PR. Overall, rates of adverse drug reactions were similar. Conclusions: OXN PR provides superior bowel function in cancer pain patients, compared with OxyPR, without compromising analgesic efficacy or safety. This study confirms that OXN PR is well tolerated and efficacious in cancer pain patients and results are in line with those seen in non-malignant pain patients. PMID:21937568

  12. Effectiveness of Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR for the Management of Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-Label, Phase 3b/4 Study.

    PubMed

    Baron, Ralf; Likar, Rudolf; Martin-Mola, Emilio; Blanco, Francisco J; Kennes, Lieven; Müller, Matthias; Falke, Dietmar; Steigerwald, Ilona

    2016-06-01

    To evaluate the effectiveness of tapentadol prolonged release (PR) vs. oxycodone/naloxone PR in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic pain component. Eligible patients (average pain intensity [numerical rating scale-3 (NRS-3)] ≥6; painDETECT positive/unclear) were randomized to twice-daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. The primary effectiveness endpoint was the change in NRS-3 from baseline to final evaluation; the exact repeated confidence interval (RCI) for tapentadol PR minus oxycodone/naloxone PR was used to establish noninferiority (upper limit <1.3) and superiority (confirmatory analyses). For the primary effectiveness endpoint, tapentadol PR was noninferior to oxycodone/naloxone PR (97.5% RCI: [-1.820, -0.184]; P < 0.001). This exact RCI also yielded evidence of superiority for tapentadol PR vs. oxycodone/naloxone PR (significantly greater reduction in pain intensity; P = 0.003). Improvements (baseline to final evaluation) in painDETECT and Neuropathic Pain Symptom Inventory scores were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (all P ≤ 0.005). The study was formally shown to be positive and demonstrated, in the primary effectiveness endpoint, the noninferiority for tapentadol PR vs. oxycodone/naloxone PR. The effectiveness of tapentadol PR was superior to that of oxycodone/naloxone PR by means of clinical relevance and statistical significance (confirmatory evidence of superiority). Tapentadol PR was associated with significantly greater improvements in neuropathic pain-related symptoms and global health status than oxycodone/naloxone PR and with a significantly better gastrointestinal tolerability profile. Tapentadol PR may be considered a first-line option for

  13. Morphine or oxycodone in cancer pain?

    PubMed

    Heiskanen, T E; Ruismäki, P M; Seppälä, T A; Kalso, E A

    2000-01-01

    Oxycodone is an opioid analgesic that closely resembles morphine. Oxymorphone, the active metabolite of oxycodone, is formed in a reaction catalyzed by CYP2D6, which is under polymorphic genetic control. The role of oxymorphone in the analgesic effect of oxycodone is not yet clear. In this study, controlled-release (CR) oxycodone and morphine were examined in cancer pain. CR oxycodone and morphine were administered to 45 adult patients with stable pain for 3-6 days after open-label titration in a randomized, double-blind, cross-over trial. Twenty patients were evaluable. Both opioids provided adequate analgesia. The variation in plasma morphine concentrations was higher than that of oxycodone, consistent with the lower bioavailability of morphine. Liver dysfunction affected selectively either oxycodone or morphine metabolism. Three patients with markedly aberrant plasma opioid concentrations are presented. Significant individual variation in morphine and oxycodone metabolism may account for abnormal responses during treatment of chronic cancer pain.

  14. Combined prolonged-release oxycodone and naloxone improves bowel function in patients receiving opioids for moderate-to-severe non-malignant chronic pain: a randomised controlled trial.

    PubMed

    Löwenstein, O; Leyendecker, P; Hopp, M; Schutter, U; Rogers, P D; Uhl, R; Bond, S; Kremers, W; Nichols, T; Krain, B; Reimer, K

    2009-03-01

    This randomised, double-blind, double-dummy, parallel-group multicentre study assessed the impact of a total daily dose of 60-80 mg oral oxycodone prolonged-release (PR)/naloxone PR (OXN PR) as fixed-ratio combination for patients with opioid-induced constipation (OIC) having moderate-to-severe, non-malignant pain. During pre-randomisation patients receiving opioids for moderate-to-severe non-malignant pain were converted to oxycodone PR (OXY PR) and titrated to an effective analgesic dose. During randomisation 265 patients on a stable OXY PR dose (60-80 mg/day) and with OIC were included in the full analysis population to receive OXN PR or OXY PR alone. Primary outcome was improvement in symptoms of constipation as measured by the Bowel Function Index (BFI). Secondary/exploratory outcomes examined analgesic efficacy and other bowel function parameters. After 4 weeks of treatment, patients receiving OXN PR showed a significant improvement in bowel function compared with those in the OXY PR group (-14.9; 95% CI: -17.9, -11.9; p<0.0001) as measured by BFI which was seen after only 1 week of treatment continuing to the end of the study. After 4 weeks of treatment, patients receiving OXN PR had a median number of 3.0 complete spontaneous bowel movements (CSBM) per week compared with only 1.0 for OXY PR alone. Laxative intake was lower in the OXN PR than the OXY PR group. Furthermore, improvements in bowel function were achieved without loss of analgesic efficacy; pain intensity scores were comparable between the groups and consistent for duration of the study. Most frequently reported adverse events were consistent with those reported for opioid analgesics; no new or unexpected adverse reactions attributable to OXN PR used in higher doses were observed. This study shows that the fixed-ratio combination of OXN PR is superior to OXY PR alone in terms of bowel function, while providing effective equivalent analgesia.

  15. Prolonged-release oxycodone-naloxone for treatment of severe pain in patients with Parkinson's disease (PANDA): a double-blind, randomised, placebo-controlled trial.

    PubMed

    Trenkwalder, Claudia; Chaudhuri, K Ray; Martinez-Martin, Pablo; Rascol, Olivier; Ehret, Reinhard; Vališ, Martin; Sátori, Maria; Krygowska-Wajs, Anna; Marti, Maria J; Reimer, Karen; Oksche, Alexander; Lomax, Mark; DeCesare, Julia; Hopp, Michael

    2015-12-01

    Pain is a common non-motor symptom of Parkinson's disease. We investigated the analgesic efficacy of prolonged-release oxycodone-naloxone (OXN PR) in patients with Parkinson's disease and chronic, severe pain. We did this phase 2 study in 47 secondary care centres in the Czech Republic, Germany, Hungary, Poland, Romania, Spain, and the UK. We enrolled patients with Hoehn and Yahr Stage II-IV Parkinson's disease, at least one type of severe pain, and an average 24-h pain score of at least 6 (assessed on an 11-point rating scale from 0=no pain to 10=pain as bad as you can imagine). Participants were randomly assigned (1:1) with a validated automated system (block size four) to either oral OXN PR or placebo for 16 weeks (starting dose oxycodone 5 mg, naloxone 2·5 mg, twice daily). Patients and investigators were masked to treatment assignment. The primary endpoint was average 24-h pain score at 16 weeks in the full analysis population. This study is registered with EudraCT (2011-002901-31) and ClinicalTrials.gov (NCT01439100). We enrolled 202 patients; 93 were assigned to OXN PR and 109 to placebo; the full analysis population consisted of 88 patients versus 106 patients. Least squares mean average 24-h pain score at 16 weeks in the full analysis population was 5·0 (95% CI 4·5 to 5·5) in the OXN PR group versus 5·6 (5·1 to 6·0) in the placebo group (difference -0·6, 95% CI -1·3 to 0·0; p=0·058). Similar proportions of patients in each group had adverse events (60/92 [65%] vs 76/109 [70%]), treatment-related adverse events (52/92 [57%] vs 62/109 [57%]), and serious adverse events (5/92 [5%] vs 7/109 [6%]). Treatment-related nausea was more common in the OXN PR group than in the placebo group (16/92 [17%] vs 10/109 [9%]), as was treatment-related constipation (16/92 [17%] vs 6/109 [6%]). The primary endpoint, based on the full analysis population at week 16, was not significant. Nonetheless, the results of this study highlight the potential efficacy of OXN PR

  16. Intractable restless legs syndrome: role of prolonged-release oxycodone-naloxone.

    PubMed

    de Biase, Stefano; Valente, Mariarosaria; Gigli, Gian Luigi

    2016-01-01

    Restless legs syndrome (RLS) is a common neurological disorder characterized by an irresistible urge to move the legs accompanied by uncomfortable sensations that occur at night or at time of rest. Pharmacological therapy should be limited to patients who suffer from clinically relevant symptoms. Chronic RLS is usually treated with either a dopamine agonist (pramipexole, ropinirole, rotigotine) or an α2δ calcium-channel ligand (gabapentin, gabapentin enacarbil, pregabalin). Augmentation is the main complication of long-term dopaminergic treatment, and frequently requires a reduction of current dopaminergic dose or a switch to non-dopaminergic medications. Opioids as monotherapy or add-on treatment should be considered when alternative satisfactory regimens are unavailable and the severity of symptoms warrants it. In a recent Phase III trial, oxycodone-naloxone prolonged release (PR) demonstrated a significant and sustained effect on patients with severe RLS inadequately controlled by previous treatments. The adverse-event profile was consistent with the safety profile of opioids. The most frequent adverse events were fatigue, constipation, nausea, headache, hyperhidrosis, somnolence, dry mouth, and pruritus. Adverse events were usually mild or moderate in intensity. No cases of augmentation were reported. Oxycodone-naloxone PR is approved for the second-line symptomatic treatment of adults with severe to very severe idiopathic RLS after failure of dopaminergic treatment. Further studies are needed to evaluate if oxycodone-naloxone PR is equally efficacious as a first-line treatment. Moreover, long-term comparative studies between opioids, dopaminergic drugs and α2δ ligands are needed.

  17. Impact of prolonged-release oxycodone/naloxone on outcomes affecting patients' daily functioning in comparison with extended-release tapentadol: a systematic review.

    PubMed

    Thakur, Deepika; Dickerson, Sara; Kumar Bhutani, Mohit; Junor, Rod

    2015-01-01

    The objective of this systematic review was to assess the clinical efficacy, safety, tolerability, and health-related quality of life outcomes associated with management of moderate-to-severe chronic pain with oxycodone/naloxone and tapentadol, focusing on the effect of these treatments on patients' daily functioning. Literature from a wide range of sources, including Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials, was searched to identify randomized controlled trials investigating tapentadol or oxycodone/naloxone for the treatment of patients with chronic pain. A network meta-analysis was conducted to determine the relative efficacy and safety profiles of these treatments. Oxycodone/naloxone was significantly better than tapentadol with respect to the Patient Assessment of Constipation Symptoms total score (risk ratio = -3.60; 95% credible interval, -5.36 to -2.11) and revealed a significantly lower risk of dizziness (risk ratio = 0.72; 95% credible interval, 0.42-0.98). Oxycodone/naloxone was directionally favored, although not significantly superior to tapentadol for headache, fatigue, dry mouth, dyspepsia, and withdrawals due to lack of efficacy. For the AE outcomes of constipation, nausea, and vomiting, as well as pain efficacy and all-cause withdrawals from studies, tapentadol was directionally favored without any statistical difference from oxycodone/naloxone. However, the two treatments were not wholly comparable for the evaluation of pain efficacy because of differences in on-study rescue medication and a higher baseline pain severity in the tapentadol studies. Oxycodone/naloxone offers significant improvements in Patient Assessment of Constipation Symptoms total score and dizziness and was directionally favored for fatigue and headache compared with extended-release tapentadol, which may translate to improved patient daily functioning and health-related quality of life. Copyright © 2015 The Authors. Published

  18. Profile of extended-release oxycodone/acetaminophen for acute pain

    PubMed Central

    Bekhit, Mary Hanna

    2015-01-01

    This article provides a historical and pharmacological overview of a new opioid analgesic that boasts an extended-release (ER) formulation designed to provide both immediate and prolonged analgesia for up to 12 hours in patients who are experiencing acute pain. This novel medication, ER oxycodone/acetaminophen, competes with current US Food and Drug Administration (FDA)-approved opioid formulations available on the market in that it offers two benefits concurrently: a prolonged duration of action, and multimodal analgesia through a combination of an opioid (oxycodone) with a nonopioid component. Current FDA-approved combination analgesics, such as Percocet (oxycodone/acetaminophen), are available solely in immediate-release (IR) formulations. PMID:26527898

  19. 77 FR 40069 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-06

    ... HUMAN SERVICES Food and Drug Administration Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration and Labeled for Human Use; Enforcement Action Dates AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA or Agency...

  20. Oral Human Abuse Potential of Oxycodone DETERx® (Xtampza® ER)

    PubMed Central

    Kopecky, Ernest A.; Levy‐Cooperman, Naama; O'Connor, Melinda; M. Sellers, Edward

    2016-01-01

    Abstract Oxycodone DETERx® (Collegium Pharmaceutical Inc, Canton, Massachusetts) is an extended‐release, microsphere‐in‐capsule, abuse‐deterrent formulation designed to retain its extended‐release properties after tampering (eg, chewing/crushing). This randomized, double‐blind, placebo‐controlled, triple‐dummy study evaluated the oral abuse potential of intact and chewed oxycodone DETERx capsules compared with crushed immediate‐release oxycodone. Subjects with a history of recreational opioid use who were nondependent/nontolerant to opioids were enrolled. Treatments included intact oxycodone DETERx (high‐fat, high‐calorie meal and fasted), chewed oxycodone DETERx (high‐fat, high‐calorie meal and fasted), crushed immediate‐release oxycodone (fasted), and placebo (high‐fat, high‐calorie meal). Plasma samples were collected to determine pharmacokinetic parameters. The primary endpoint was drug liking at the moment; other endpoints included drug effects questionnaire scores, Addiction Research Center Inventory/Morphine Benzedrine Group score, pupillometry measurements, and safety. Thirty‐eight subjects completed the study. Chewed and intact oxycodone DETERx were bioequivalent, unlike crushed immediate‐release oxycodone, which yielded higher peak oxycodone plasma concentrations compared with all methods of oxycodone DETERx administration. The mean maximum (peak) effect (Emax) for drug liking was significantly lower for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .01). The time to Emax was significantly longer for chewed and intact oxycodone DETERx than for crushed immediate‐release oxycodone (P < .0001). Scores for feeling high and Addiction Research Center Inventory/Morphine Benzedrine Group scores demonstrated lower abuse potential for chewed and intact oxycodone DETERx compared with crushed immediate‐release oxycodone. Study treatments were well tolerated; no subjects experienced

  1. Oral Human Abuse Potential of Oxycodone DETERx(®) (Xtampza(®) ER).

    PubMed

    Kopecky, Ernest A; Fleming, Alison B; Levy-Cooperman, Naama; O'Connor, Melinda; M Sellers, Edward

    2017-04-01

    Oxycodone DETERx(®) (Collegium Pharmaceutical Inc, Canton, Massachusetts) is an extended-release, microsphere-in-capsule, abuse-deterrent formulation designed to retain its extended-release properties after tampering (eg, chewing/crushing). This randomized, double-blind, placebo-controlled, triple-dummy study evaluated the oral abuse potential of intact and chewed oxycodone DETERx capsules compared with crushed immediate-release oxycodone. Subjects with a history of recreational opioid use who were nondependent/nontolerant to opioids were enrolled. Treatments included intact oxycodone DETERx (high-fat, high-calorie meal and fasted), chewed oxycodone DETERx (high-fat, high-calorie meal and fasted), crushed immediate-release oxycodone (fasted), and placebo (high-fat, high-calorie meal). Plasma samples were collected to determine pharmacokinetic parameters. The primary endpoint was drug liking at the moment; other endpoints included drug effects questionnaire scores, Addiction Research Center Inventory/Morphine Benzedrine Group score, pupillometry measurements, and safety. Thirty-eight subjects completed the study. Chewed and intact oxycodone DETERx were bioequivalent, unlike crushed immediate-release oxycodone, which yielded higher peak oxycodone plasma concentrations compared with all methods of oxycodone DETERx administration. The mean maximum (peak) effect (Emax ) for drug liking was significantly lower for chewed and intact oxycodone DETERx than for crushed immediate-release oxycodone (P < .01). The time to Emax was significantly longer for chewed and intact oxycodone DETERx than for crushed immediate-release oxycodone (P < .0001). Scores for feeling high and Addiction Research Center Inventory/Morphine Benzedrine Group scores demonstrated lower abuse potential for chewed and intact oxycodone DETERx compared with crushed immediate-release oxycodone. Study treatments were well tolerated; no subjects experienced serious adverse events. These results demonstrate

  2. [Cost-effective analysis of rotation from sustained-release morphine tablet to transdermal fentanyl of matrix type or sustained-release oxycodone tablet].

    PubMed

    Ise, Yuya; Wako, Tetsuya; Miura, Yoshihiko; Katayama, Shirou; Shimizu, Hisanori

    2009-12-01

    The present study was undertaken to determine the pharmacoeconomics of switching from sustained-release morphine tablet to matrix type (MT) of transdermal fontanel or sustained-release Oxycodone tablet. Cost-effective analysis was performed using a simulation model along with decision analysis. The analysis was done from the payer's perspective. The cost-effective ratio/patient of transdermal MT fontanel (22, 539 yen)was lower than that of sustained -release Oxycodone tablet (23, 630 yen), although a sensitivity analysis could not indicate that this result was reliable. These results suggest the possibility that transdermal MT fontanel was much less expensive than a sustained-release Oxycodone tablet.

  3. A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment.

    PubMed

    Rauck, Richard L; Hale, Martin E; Bass, Almasa; Bramson, Candace; Pixton, Glenn; Wilson, Jacquelyn G; Setnik, Beatrice; Meisner, Paul; Sommerville, Kenneth W; Malhotra, Bimal K; Wolfram, Gernot

    2015-09-01

    The objective of this multicenter, double-blind, placebo-controlled, randomized withdrawal study was to evaluate the efficacy and safety of ALO-02, an abuse-deterrent formulation containing pellets of extended-release oxycodone hydrochloride (HCl) surrounding sequestered naltrexone HCl, compared with placebo in the treatment of moderate-to-severe chronic low back pain. An open-label titration period in which all patients received ALO-02 was followed by a double-blind treatment period where patients meeting treatment response criteria were randomized to either a fixed dose of ALO-02 or placebo. Daily average low back pain was assessed using an 11-point numeric rating scale (NRS)-Pain. Of the 663 patients screened, 410 received ALO-02 during the open-label conversion and titration period and 281 patients were randomized to the double-blind treatment period (n = 134, placebo; n = 147, ALO-02). Change in the mean NRS-Pain score from randomization baseline to the final 2 weeks of the treatment period was significantly different favoring ALO-02 compared with placebo (P = 0.0114). Forty-four percent of patients treated with placebo and 57.5% of patients treated with ALO-02 reported ≥30% improvement in weekly average NRS-Pain scores from screening to the final 2 weeks of the treatment period (P = 0.0248). In the double-blind treatment period, 56.8% of patients in the ALO-02 group and 56.0% of patients in the placebo group experienced a treatment-emergent adverse event (TEAE). The most common treatment-related TEAEs for ALO-02 during the treatment period were nausea, vomiting, and constipation, consistent with opioid therapy. ALO-02 has been demonstrated to provide significant reduction of pain in patients with chronic low back pain and has a safety profile similar to other opioids.

  4. The effect of single-dose tramadol on oxycodone clearance.

    PubMed

    Curry, Steven C; Watts, David J; Katz, Kenneth D; Bikin, Dale; Bukaveckas, Bonny L

    2007-11-01

    We have noticed increased prescribing of tramadol by emergency physicians for breakthrough pain in patients chronically taking oxycodone. Both oxycodone and tramadol undergo oxidative metabolism by CYP2D6 and CYP3A4, suggesting the possibility that tramadol may compete with oxycodone for metabolism. A randomized controlled trial in 10 human volunteers was performed to determine if single-dose tramadol therapy would impair oxycodone clearance. Subjects were randomized whether to enter the control or experimental arm of the study first, with each subject serving as his or her own control. In the control arm, each subject received 10 mg immediate-release oxycodone orally and had serial plasma oxycodone and oxymorphone concentrations measured over 8 h. The experimental arm was identical except that 100 mg tramadol was ingested 1.5 h before oxycodone. Clearance divided by fraction absorbed (CL/f) was calculated using the dose and the area under the 8-h time-plasma oxycodone concentration curve. Peak plasma oxycodone concentrations (C(max)) and time until peak oxycodone concentrations (T(max)) were secondary outcome parameters. Group size was chosen to produce a power of 0.8 to detect a 20% difference in CL/f between study arms. Values for CL/f, C(max), and T(max) were compared between study arms using two-tailed, paired t-tests. No statistically significant difference between groups was demonstrated for any parameter. We failed to demonstrate that single doses of tramadol impaired oxycodone clearance.

  5. Changes in oxycodone and heroin exposures in the National Poison Data System after introduction of extended-release oxycodone with abuse-deterrent characteristics.

    PubMed

    Coplan, Paul M; Kale, Hrishikesh; Sandstrom, Lauren; Landau, Craig; Chilcoat, Howard D

    2013-12-01

    Abuse and misuse of prescription opioids are serious public health problems. Abuse-deterrent formulations are an intervention to balance risk mitigation with appropriate patient access. This study evaluated the effects of physicochemical barriers to crushing and dissolving on safety outcomes associated with extended-release oxycodone (ERO) tablets (OxyContin) using a national surveillance system of poison centers. Other single-entity (SE) oxycodone tablets and heroin were used as comparators and to assess substitution effects. The National Poison Data System covering all US poison centers was used to measure changes in exposures in the year before versus the 2 years after introduction of reformulated ERO (7/2009-6/2010 vs 9/2010-9/2012). Outcomes included abuse, therapeutic errors affecting patients, and accidental exposures. After ERO reformulation, abuse exposures decreased 36% for ERO, increased 20% for other SE oxycodone, and increased 42% for heroin. Therapeutic errors affecting patients decreased 20% for ERO and increased 19% for other SE oxycodone. Accidental exposures decreased 39% for ERO, increased 21% for heroin, and remained unchanged for other SE oxycodone. During the study period, other interventions to reduce opioid abuse occurred, for example, educational and prescription monitoring programs. However, these have shown small effects and do not explain a drop for ERO exposures but not for other opioids. After ERO reformulation, calls to poison centers involving abuse, therapeutic errors affecting patients, and accidental exposures decreased for ERO, but not for comparator opioids. Abuse-deterrent formulations of opioid analgesics can reduce abuse, but switching to other accessible non abuse-deterrent opioids might occur. © 2013 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

  6. Developments in managing severe chronic pain: role of oxycodone-naloxone extended release.

    PubMed

    Fanelli, Guido; Fanelli, Andrea

    2015-01-01

    Chronic pain is a highly disabling condition, which can significantly reduce patients' quality of life. Prevalence of moderate and severe chronic pain is high in the general population, and it increases significantly in patients with advanced cancer and older than 65 years. Guidelines for the management of chronic pain recommend opioids for the treatment of moderate-to-severe pain in patients whose pain is not responsive to initial therapies with paracetamol and/or nonsteroidal anti-inflammatory drugs. Despite their analgesic efficacy being well recognized, adverse events can affect daily functioning and patient quality of life. Opioid-induced constipation (OIC) occurs in 40% of opioid-treated patients. Laxatives are the most common drugs used to prevent and treat OIC. Laxatives do not address the underlying mechanisms of OIC; for this reason, they are not really effective in OIC treatment. Naloxone is an opioid receptor antagonist with low systemic bioavailability. When administered orally, naloxone antagonizes the opioid receptors in the gut wall, while its extensive first-pass hepatic metabolism ensures the lack of antagonist influence on the central-mediated analgesic effect of the opioids. A prolonged-release formulation consisting of oxycodone and naloxone in a 2:1 ratio was developed trying to reduce the incidence of OIC maintaining the analgesic effect compared with use of the sole oxycodone. This review includes evidence related to use of oxycodone and naloxone in the long-term management of chronic non-cancer pain and OIC.

  7. Decreased diversion by doctor-shopping for a reformulated extended release oxycodone product (OxyContin).

    PubMed

    Chilcoat, Howard D; Coplan, Paul M; Harikrishnan, Venkatesh; Alexander, Louis

    2016-08-01

    Doctor-shopping (obtaining prescriptions from multiple prescribers/pharmacies) for opioid analgesics produces a supply for diversion and abuse, and represents a major public health issue. An open cohort study assessed changes in doctor-shopping in the U.S. for a brand extended release (ER) oxycodone product (OxyContin) and comparator opioids before (July, 2009 to June, 2010) versus after (January, 2011 to June, 2013) introduction of reformulated brand ER oxycodone with abuse-deterrent properties, using IMS LRx longitudinal data covering >150 million patients and 65% of retail U.S. prescriptions. After its reformulation, the rate of doctor-shopping decreased 50% (for 2+ prescribers/3+ pharmacies) for brand ER oxycodone, but not for comparators. The largest decreases in rates occurred among young adults (73%), those paying with cash (61%) and those receiving the highest available dose (62%), with a 90% decrease when stratifying by all three characteristics. The magnitude of doctor-shopping reductions increased with increasing number of prescribers/pharmacies (e.g., 75% reduction for ≥2 prescribers/≥4 pharmacies). The rate of doctor-shopping for brand ER oxycodone decreased substantially after its reformulation, which did not occur for other prescription opioids. The largest reductions in doctor-shopping occurred with characteristics associated with higher abuse risk such as youth, cash payment and high dose, and with more specific thresholds of doctor-shopping. A higher prescriber and/or pharmacy threshold also increased the magnitude of the decrease, suggesting that it better captured the effect of the reformulation on actual doctor-shoppers. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Tolerability, Safety, and Quality of Life with Tapentadol Prolonged Release (PR) Compared with Oxycodone/Naloxone PR in Patients with Severe Chronic Low Back Pain with a Neuropathic Component: A Randomized, Controlled, Open-label, Phase 3b/4 Trial.

    PubMed

    Baron, Ralf; Jansen, Jan-Peter; Binder, Andreas; Pombo-Suarez, Manuel; Kennes, Lieven; Müller, Matthias; Falke, Dietmar; Steigerwald, Ilona

    2016-06-01

    To evaluate tolerability, safety, and quality-of-life outcomes in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic component receiving tapentadol PR vs. oxycodone/naloxone PR. Eligible patients (average pain intensity [numerical rating scale] ≥ 6; painDETECT positive/unclear ratings) were randomized to twice-daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. Change in the Patient Assessment of Constipation Symptoms (PAC-SYM) total score from baseline to final evaluation was a primary endpoint. For the primary tolerability-related endpoint, the 97.5% exact repeated confidence interval for tapentadol PR minus oxycodone/naloxone PR for the PAC-SYM total score was [-0.259, 0.121], showing noninferiority (upper limit < 0.7). Incidences of constipation and vomiting were significantly lower with tapentadol PR than oxycodone/naloxone PR (P ≤ 0.045). Confirmatory superiority based on formal noninferiority was shown for the primary effectiveness endpoint (change from baseline to final evaluation in pain intensity) for tapentadol PR vs. oxycodone/naloxone PR (presented separately). Improvements in the Short Form-12 physical component summary and EuroQol-5 Dimension health status index and health state assessment were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (P ≤ 0.024). Tapentadol PR had a minimal impact on bowel function (noninferior to oxycodone/naloxone PR) and, along with superior effectiveness (presented separately), was associated with significantly lower incidences of constipation and vomiting and significant improvements in quality-of-life measures vs. oxycodone/naloxone PR. © 2015 The authors. Pain Practice published by Wiley Periodicals, Inc. on behalf of World Institute of Pain.

  9. Efficacy and tolerability of oxycodone versus fentanyl for intravenous patient-controlled analgesia after gastrointestinal laparotomy

    PubMed Central

    Ding, Zhen; Wang, Kaiguo; Wang, Baosheng; Zhou, Naibao; Li, Hao; Yan, Bo

    2016-01-01

    Abstract Background: It has been suggested that oxycodone is effective in relieving acute postoperative pain. The aim of this study was to investigate the efficacy and tolerability of oxycodone (O) versus fentanyl (F), and the adequate potency ratio of oxycodone and fentanyl in patients with intravenous patient-controlled analgesia after gastric laparotomy. Methods: In this double-blinded, randomized, controlled study, 60 patients undergoing elective gastric laparotomy were allocated to receive either oxycodone or fentanyl for postoperative intravenous patient-controlled analgesia (potency ratio 60:1). The patients received ketorolac 60 mg before the end of anesthesia and then continued with patient-controlled analgesia for 48 hours postsurgery. Pain severity, side effects and respiration rate were recorded 30 minutes, 3, 6, 12, 24, and 48 hours after the surgery. Cumulative opioid requirements and patient satisfaction were also measured. Results: The median consumption more than 48 hours after operation of oxycodone was 50 mg (range: 40.0–62.4 mg) and fentanyl was 0.8 mg (range: 0.6–1.1 mg), and the percentage of patients requiring rescue medication was not statistically significant. Numeric rating scores at rest and upon movement were significantly lower in group O than in F (P < 0.05). Whereas the incidences of adverse events were similar between the groups (33.3% vs 27.6%, P = 0.64), a significant higher sedation scores were found in patients given fentanyl at 30 minutes after the surgery (P = 0.04). Conclusion: Oxycodone was comparable to fentanyl in the relief of postoperative pain following gastric laparotomy. Oxycodone not only provides better postoperative pain relief and less sedation, but also there was a tendency toward more side effects with oxycodone. PMID:27684835

  10. The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone

    PubMed Central

    Samer, CF; Daali, Y; Wagner, M; Hopfgartner, G; Eap, CB; Rebsamen, MC; Rossier, MF; Hochstrasser, D; Dayer, P; Desmeules, JA

    2010-01-01

    Background and purpose: There is high interindividual variability in the activity of drug-metabolizing enzymes catalysing the oxidation of oxycodone [cytochrome P450 (CYP) 2D6 and 3A], due to genetic polymorphisms and/or drug–drug interactions. The effects of CYP2D6 and/or CYP3A activity modulation on the pharmacokinetics of oxycodone remains poorly explored. Experimental approach: A randomized crossover double-blind placebo-controlled study was performed with 10 healthy volunteers genotyped for CYP2D6 [six extensive (EM), two deficient (PM/IM) and two ultrarapid metabolizers (UM)]. The volunteers randomly received on five different occasions: oxycodone 0.2 mg·kg−1 and placebo; oxycodone and quinidine (CYP2D6 inhibitor); oxycodone and ketoconazole (CYP3A inhibitor); oxycodone and quinidine+ketoconazole; placebo. Blood samples for plasma concentrations of oxycodone and metabolites (oxymorphone, noroxycodone and noroxymorphone) were collected for 24 h after dosing. Phenotyping for CYP2D6 (with dextromethorphan) and CYP3A (with midazolam) were assessed at each session. Key results: CYP2D6 activity was correlated with oxymorphone and noroxymorphone AUCs and Cmax (−0.71 < Spearman correlation coefficient ρs < −0.92). Oxymorphone Cmax was 62% and 75% lower in PM than EM and UM. Noroxymorphone Cmax reduction was even more pronounced (90%). In UM, oxymorphone and noroxymorphone concentrations increased whereas noroxycodone exposure was halved. Blocking CYP2D6 (with quinidine) reduced oxymorphone and noroxymorphone Cmax by 40% and 80%, and increased noroxycodone AUC∞ by 70%. Blocking CYP3A4 (with ketoconazole) tripled oxymorphone AUC∞ and reduced noroxycodone and noroxymorphone AUCs by 80%. Shunting to CYP2D6 pathway was observed after CYP3A4 inhibition. Conclusions and implications: Drug–drug interactions via CYP2D6 and CYP3A affected oxycodone pharmacokinetics and its magnitude depended on CYP2D6 genotype. PMID:20590587

  11. Safety and Tolerability of Biphasic Immediate-Release/Extended-Release Oxycodone/Acetaminophen Tablets: Analysis of 11 Clinical Trials.

    PubMed

    Barrett, Thomas; Kostenbader, Kenneth; Nalamachu, Srinivas; Giuliani, Michael; Young, Jim L

    2016-09-01

    To characterize the safety of immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP). Data were assessed from 9 phase 1 trials in healthy volunteers and recreational users of prescription opioids (N = 405), including 5 single-dose and 3 multidose open-label pharmacokinetic studies of IR/ER OC/APAP and active comparators; and 1 randomized, controlled, single-dose human abuse potential (HAP) study comparing IR/ER OC/APAP, IR OC/APAP, and placebo in recreational users of opioids; and 2 phase 3 trials (N = 701) including a 48-hour placebo-controlled safety and efficacy study in patients with moderate to severe postbunionectomy pain with a 14-day open-label safety extension and a long-term (≤ 35 days) open-label safety study in patients with chronic osteoarthritis pain or chronic low back pain. Adverse events (AEs) experienced by ≥ 10% of participants receiving IR/ER OC/APAP in all trials were pruritus, nausea, vomiting, dizziness, headache, and somnolence; these AEs occurred with similar frequency for equianalgesic doses of IR OC/APAP and IR OC but less frequently for IR tramadol HCl/APAP. In the HAP study, crushing IR/ER or IR OC/APAP tablets did not increase frequency of AEs. Constipation was experienced by < 10% of participants receiving IR/ER OC/APAP. No serious (SAE) or severe AEs were reported in phase 1 trials. In phase 3 trials of 8 reported SAEs, only 1 treatment-related SAE (hypersensitivity to placebo) required treatment discontinuation. No clinically meaningful changes in vital signs, oxygen saturation, electrocardiograms, or laboratory values were reported. Safety and tolerability of IR/ER OC/APAP are similar to other low-dose opioid/APAP analgesics. © 2015 World Institute of Pain.

  12. A randomised, placebo-controlled trial comparing the effects of tapentadol and oxycodone on gastrointestinal and colonic transit in healthy humans.

    PubMed

    Jeong, I D; Camilleri, M; Shin, A; Iturrino, J; Boldingh, A; Busciglio, I; Burton, D; Ryks, M; Rhoten, D; Zinsmeister, A R

    2012-05-01

    Tapentadol is a mu-opioid receptor agonist and norepinephrine reuptake inhibitor. In clinical trials, tapentadol provided somatic pain relief comparable to mu-opioids such as oxycodone, with significantly less gastrointestinal adverse effects. The acute effects of tapentadol on gastrointestinal and colonic transit are unclear. To compare acute effects of oral tapentadol and oxycodone on gastric, small bowel and colonic transit of solids in 38 healthy human subjects. In a randomised, parallel-group, double-blind, placebo-controlled study of the effects of identical-appearing tapentadol immediate release (IR), 75 mg t.d.s., or oxycodone IR, 5 mg t.d.s., for 48 h, we measured gastric (GE), small bowel (SBT measured as colonic filling at 6 h) and colonic transit by validated scintigraphy. Drug was commenced on the evening before the start of the transit test. The primary endpoints were overall colonic transit (geometric centre, GC) at 24 h and GE half-time (t1/2 ). ancova of transit data included gender or BMI as covariates. Adverse effects were summarised. At the doses tested, oxycodone and tapentadol significantly delayed GE t1/2 and SBT, but not overall colonic transit, compared to placebo. Transit profiles in all regions were not significantly different between oxycodone and tapentadol at the doses tested. Both oxycodone and tapentadol were associated with nausea and central effects attributable to central opiate effects. Tapentadol significantly delayed gastric emptying t1/2 and small bowel transit, similar to oxycodone. These data suggest that acute administration of tapentadol may not have significant advantages over standard mu-opioids, in terms of the potential to avoid upper gastrointestinal motor dysfunction. © 2012 Blackwell Publishing Ltd.

  13. Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets

    PubMed Central

    Franke, Ryan M; Morton, Terri; Devarakonda, Krishna

    2015-01-01

    This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions and the effects of a meal on their single-dose population PK. Data were pooled from four randomized, single-dose crossover trials enrolling healthy adult (18–55 years old) participants (three trials) and nondependent recreational users of prescription opioids (one trial) with a body weight of ≥59 kg. Participants received IR/ER OC/APAP 7.5/325 mg tablets in single doses of 7.5/325 mg (one tablet), 15/650 mg (two tablets), or 30/1,300 mg (four tablets) under fasted or fed conditions. Six variables were examined: sex, race, age, weight, height, and body mass index. Single-dose population PK was analyzed using first-order conditional estimation methods. A total of 151 participants were included in the analysis under fasted conditions, and 31 participants were included in the fed analysis. Under fasted conditions, a 10% change in body weight was accompanied by ~7.5% change in total body clearance (CL/F) and volume of distribution (V/F) of OC and APAP. Black participants had 17.3% lower CL/F and a 16.9% lower V/F of OC compared with white participants. Under fed conditions, the absorption rate constant of OC and APAP decreased significantly, although there was no effect on CL/F and V/F. Considering that the recommended dose for IR/ER OC/APAP 7.5/325 mg tablets is two tablets every 12 hours, adjustments of <50% are not clinically relevant. Dose adjustment may be necessary for large deviations from average body weight, but the small PK effects associated with race and consumption of a meal are not clinically relevant. PMID:26316698

  14. Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets.

    PubMed

    Franke, Ryan M; Morton, Terri; Devarakonda, Krishna

    2015-01-01

    This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions and the effects of a meal on their single-dose population PK. Data were pooled from four randomized, single-dose crossover trials enrolling healthy adult (18-55 years old) participants (three trials) and nondependent recreational users of prescription opioids (one trial) with a body weight of ≥59 kg. Participants received IR/ER OC/APAP 7.5/325 mg tablets in single doses of 7.5/325 mg (one tablet), 15/650 mg (two tablets), or 30/1,300 mg (four tablets) under fasted or fed conditions. Six variables were examined: sex, race, age, weight, height, and body mass index. Single-dose population PK was analyzed using first-order conditional estimation methods. A total of 151 participants were included in the analysis under fasted conditions, and 31 participants were included in the fed analysis. Under fasted conditions, a 10% change in body weight was accompanied by ~7.5% change in total body clearance (CL/F) and volume of distribution (V/F) of OC and APAP. Black participants had 17.3% lower CL/F and a 16.9% lower V/F of OC compared with white participants. Under fed conditions, the absorption rate constant of OC and APAP decreased significantly, although there was no effect on CL/F and V/F. Considering that the recommended dose for IR/ER OC/APAP 7.5/325 mg tablets is two tablets every 12 hours, adjustments of <50% are not clinically relevant. Dose adjustment may be necessary for large deviations from average body weight, but the small PK effects associated with race and consumption of a meal are not clinically relevant.

  15. [Case of acute exacerbation of neuropathic cancer pain rapidly relieved by simultaneous oral intake of immediate release oxycodone and pregabalin].

    PubMed

    Baba, Mika; Gomwo, Ikuo

    2012-10-01

    Cancer pain consists of continuous pain lasting almost all day and transient exacerbation of pain called breakthrough pain. Breakthrough pain is classified as somatic pain and visceral pain, neuropathic pain according to the character of pain. Although the immediate release opioid is used as the first treatment of choice to breakthrough pain, the effect is not enough when it shows the character of neuropathic pain. Pregabalin has become the first medicine for the treatment of neuropathic pain, and it sometimes reveals prompt analgesic effect based on its pharmacological profile. It has also been reported that pregabalin used with oxycodine reveals analgesic effect with smaller dosage than pregabalin alone. We experienced a young patient with lung cancer suffering from sudden exacerbation of symptomatic sciatica, whose pain was markedly reduced within 30 minutes by taking immediate release oxycodone 5 mg and pregabalin 75 mg simultaneously. Conclusions : Pregabalin with immediate release oxycodone simultaneously may be able to improve acute exacerbation of neuropathic cancer pain rapidly.

  16. Correlation of Subjective Effects with Systemic Opioid Exposure from Fixed-Dose Combinations of Oxycodone/Acetaminophen in Recreational Users of Prescription Drugs.

    PubMed

    Morton, Terri L; Devarakonda, Krishna; Kostenbader, Kenneth; Montgomery, Jeannie; Barrett, Thomas; Webster, Lynn

    2016-03-01

    To correlate abuse-related pharmacodynamic measures and pharmacokinetic measures after administering immediate-release/extended-release and immediate-release oxycodone/acetaminophen fixed-dose combination analgesicsDesign. Randomized, double-blind, active- and placebo-controlled, 7-way crossover studySetting. Contract research organizationSubjects. Nondependent recreational users of prescription opioids. Participants received single doses of intact immediate-release/extended-release and immediate-release oxycodone/acetaminophen 15/650 mg, intact immediate-release/extended-release and immediate-release oxycodone/acetaminophen 30/1,300 mg, crushed immediate-release/extended-release and immediate-release oxycodone/acetaminophen 30/1,300 mg, and placebo. Measures of pharmacodynamics (pupillometry, drug liking, drug high, good drug effects) and pharmacokinetics were assessed predose and up to 24 hours postdose, and correlations between pharmacokinetic parameters and pharmacodynamic data were explored. Of 61 participants, 55 completed all 7 treatments. Intact immediate-release/extended-release oxycodone/acetaminophen produced 50% lower oxycodone peak plasma concentration (Cmax) than immediate-release oxycodone/acetaminophen. Median oxycodone time to Cmax (tmax) was significantly longer (P<0.001) for intact immediate-release/extended-release oxycodone/acetaminophen than immediate-release oxycodone/acetaminophen. The pharmacokinetics of crushed immediate-release/extended-release and immediate-release oxycodone/acetaminophen (30/1,300 mg) followed a similar pattern. Crushing did not shorten the median oxycodone tmax for immediate-release/extended-release oxycodone/acetaminophen (30/1,300 mg). Strong correlations were observed between oxycodone Cmax and area under the curve from time 0 to time x peak effects and area under the subjective effect curve from time 0 to time x for all subjective effects (R(2)=0.711-0.997). Immediate-release/extended-release oxycodone

  17. Pooled Post Hoc Analysis of Population Pharmacokinetics of Oxycodone and Acetaminophen Following Multiple Oral Doses of Biphasic Immediate-Release/Extended-Release Oxycodone/Acetaminophen Tablets.

    PubMed

    Morton, Terri; Franke, Ryan; Devarakonda, Krishna

    2016-07-01

    To examine whether biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325-mg tablets have clinically relevant variability in population pharmacokinetics (PK). Post hoc analysis of 2 phase 1 randomized, open-label, multiple-dose crossover studies. Single contract research organization clinic. Men and women aged 18 to 55 years with a body mass index of 19 to 30 kg/m(2) and body weight ≥ 59 kg. Fasted participants (N = 96) received 2 tablets of IR/ER OC/APAP 7.5/325 mg (total dose, 15/650 mg) every 12 hours for 4.5 days. Population PK analysis was performed using nonlinear mixed effects modeling and evaluated 6 population variables. The average PK estimates for OC were 75 L/hour for clearance (CL/F), 756 L for volume of distribution (V/F), and 0.581 per hour for absorption rate constant (Ka ). Body weight was a statistically significant source of variability in V/F for OC at steady state. Average estimates for APAP were 25 L/hour for CL/F and 119 L for V/F. Sex was identified as a statistically significant source of variability in CL/F with predicted values for APAP of 25 L/hour in men and 21 L/hour in women. Body weight affected variability in V/F, with a predicted value of 193 L in men and 174 L in women for a 72-kg participant at steady state. Dose adjustments of < 50% are not clinically relevant for IR/ER OC/APAP 7.5/325-mg tablets considering the approved dose of 1 to 2 tablets every 8 to 12 hours; thus, adjustment may be necessary for large deviations from normal body weight but not for sex. © 2015 World Institute of Pain.

  18. Oxycodone with an opioid receptor antagonist: A review.

    PubMed

    Davis, Mellar P; Goforth, Harold W

    2016-01-01

    The rationale for putting opioid antagonists with an agonist is to improve pain control, to reduce side effects, and/or to reduce abuse. The combination of prolonged release (PR) oxycodone and naloxone reduces constipation as demonstrated in multiple studies and has been designated a tamper-resistant opioid by the Food and Drug Administration. Bioequivalence of the combination product compared with PR oxycodone has not been established. Several of the pivotal studies provided suboptimal laxative support in the control arm of the randomized trials. Two noninferiority trials have demonstrated equivalent analgesia between PR oxycodone and the combination product at doses of less than 120 mg of oxycodone per day. There appears to be an analgesic ceiling above 80-120 mg of oxycodone per day. Safety monitoring during randomized trials was not been well described in published manuscripts. Benefits appear to be better for those with chronic noncancer pain compared with individuals with cancer when constipation was the primary outcome.

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

    PubMed

    Coluzzi, F; Mattia, C

    2005-01-01

    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.

  20. Oxycodone versus fentanyl for intravenous patient-controlled analgesia after laparoscopic supracervical hysterectomy

    PubMed Central

    Kim, Nan Seol; Lee, Jeong Seok; Park, Su Yeon; Ryu, Aeli; Chun, Hea Rim; Chung, Ho Soon; Kang, Kyou Sik; Chung, Jin Hun; Jung, Kyung Taek; Mun, Seong Taek

    2017-01-01

    Abstract Background: Oxycodone, a semisynthetic thebaine derivative opioid, is widely used for the relief of moderate to severe pain. The aim of this study was to compare the efficacy and side effects of oxycodone and fentanyl in the management of postoperative pain by intravenous patient-controlled analgesia (IV-PCA) in patients who underwent laparoscopic supracervical hysterectomy (LSH). Methods: The 127 patients were randomized to postoperative pain treatment with either oxycodone (n = 64, group O) or fentanyl group (n = 63, group F). Patients received 7.5 mg oxycodone or 100 μg fentanyl with 30-mg ketorolac at the end of anesthesia followed by IV-PCA (potency ratio 75:1) for 48 hours postoperatively. A blinded observer assessed postoperative pain based on the numerical rating scale (NRS), infused PCA dose, patient satisfaction, sedation level, and side effects. Results: Accumulated IV-PCA consumption in group O was less (63.5 ± 23.9 mL) than in group F (85.3 ± 2.41 mL) during the first 48 hours postoperatively (P = 0.012). The NRS score of group O was significantly lower than that of group F at 4 and 8 hours postoperatively (P < .001); however, the incidence of postoperative nausea and vomiting (PONV), dizziness, and drowsiness was significantly higher in group O than in group F. Patient satisfaction was lower in group O than in group F during the 48 hours after surgery (P < 0.001). Conclusions: Oxycodone IV-PCA (potency ratio 1:75) provided superior analgesia to fentanyl IV-PCA after LSH; however, the higher incidence of side effects, including PONV, dizziness, and drowsiness, suggests that the doses used in this study were not equipotent. PMID:28272250

  1. Effect of prolonged-released oxycodone/naloxone in postoperative pain management after total knee replacement: a nonrandomized prospective trial.

    PubMed

    Oppermann, Johannes; Bredow, Jan; Spies, Christian K; Lemken, Julia; Unglaub, Frank; Boese, Christoph K; Dargel, Jens; Eysel, Peer; Zöllner, Jan

    2016-09-01

    The purpose of this study was to examine the effect of postoperative prolonged release oxycodone/naloxone (OXN) in comparison to other opioids (control group) on the early postoperative rehabilitation outcome after total knee replacement. In a prospective, noninterventional, nonrandomized clinical trial, 80 patients were assigned to either the OXN group or a control group. Postoperative outcome and pain level at days 3, 6, 21, 35, and 6months were evaluated using the Bowel Function Index, Brief Pain Inventory Short Form questionnaire, the Hospital for Special Surgery score, modified Larson score, and the ability to attend physiotherapy. Medications were recorded and safety analysis was done. Both groups were compared using an analysis of covariance. There were no significant differences between both groups regarding pain levels. OXN group patients reported better bowel function (median values of 0.0 for the OXN group and 20.0 for the control group). No effect of treatment group (P=.19) and no treatment-by-visit interaction on Hospital for Special Surgery final score (P=.67) could be detected, but Larson function score in the early postoperative phase was significantly better in the OXN group (P=.018). The proportion of OXN group patients who were able to attend without any restriction was 58.1%. The proportions of patients in the OXN group and control group who experienced mild or moderate adverse drug reactions were 23.3% and 37.8%, respectively. There were no serious adverse drug reactions. In conclusion, OXN provides an effective analgesia and offers several benefits such as higher ability to participate in physiotherapy and better functional results. Incidence and severity of constipation can be reduced by using prolonged-released OXN as compared with other opioids. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Comparison of the analgesic effect of patient-controlled oxycodone and fentanyl for pain management in patients undergoing colorectal surgery.

    PubMed

    Jung, Kyeo-Woon; Kang, Hyeon-Wook; Park, Chan-Hye; Choi, Byung-Hyun; Bang, Ji-Yeon; Lee, Soo-Han; Lee, Eun-Kyung; Choi, Byung-Moon; Noh, Gyu-Jeong

    2016-08-01

    Oxycodone is a μ-opioid receptor agonist and is generally indicated for the relief of moderate to severe pain. The aim of this study was to compare the analgesic efficacy of patient-controlled oxycodone and fentanyl for postoperative pain in patients undergoing colorectal surgery. Patients scheduled to undergo elective colorectal surgery (n=82) were allocated to receive oxycodone (n=41, concentration of 1 mg/mL) or fentanyl (n=41, concentration of 15 μg/mL) for postoperative pain management. After the operation, pain using a numerical rating scale (NRS), delivery to demand ratio, infused dose of patient-controlled analgesia (PCA), side effects, and sedation levels were evaluated. Median (25%-75%) cumulative PCA dose of oxycodone group at 48 hours (66.9, 58.4-83.7 mL) was significantly less than that of fentanyl group (80.0, 63.4-103.3 mL, P=.037). Six hours after surgery, the mean (SD) NRS scores of the oxycodone and fentanyl groups were 6.2 (2.4) and 6.8 (1.9), respectively (P=.216). The mean equianalgesic potency ratio of oxycodone to fentanyl was 55:1. The groups did not differ in postoperative nausea, vomiting, and level of sedation. Patient-controlled oxycodone provides similar effects for pain relief compared to patient-controlled fentanyl in spite of less cumulative PCA dose. Based on these results, oxycodone can be a useful alternative to fentanyl for PCA in patients after colorectal surgery. © 2016 John Wiley & Sons Australia, Ltd.

  3. Reduced abuse, therapeutic errors, and diversion following reformulation of extended-release oxycodone in 2010.

    PubMed

    Severtson, Stevan Geoffrey; Bartelson, Becki Bucher; Davis, Jonathan M; Muñoz, Alvaro; Schneider, Michael F; Chilcoat, Howard; Coplan, Paul M; Surratt, Hilary; Dart, Richard C

    2013-10-01

    This study evaluated changes in abuse exposures, therapeutic error exposures, and diversion into illegal markets associated with brand extended-release oxycodone (ERO) following introduction of reformulated ERO. Original ERO and reformulated ERO street prices also were compared. Data from the Poison Center and Drug Diversion programs of the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System were used. Quarterly rates 2 years prior to introduction of reformulated ERO (October 2008 through September 2010) were compared to quarterly rates after introduction (October 2010 through March 2012) using negative binomial regression. Street prices were compared using a mixed effects linear regression model. Following reformulated ERO introduction, poison center ERO abuse exposures declined 38% (95% confidence interval [CI]: 31-45) per population and 32% (95% CI: 24-39) per unique recipients of dispensed drug. Therapeutic error exposures declined 24% (95% CI: 15-31) per population and 15% (95% CI: 6-24) per unique recipients of dispensed drug. Diversion reports declined 53% (95% CI: 41-63) per population and 50% (95% CI: 39-59) per unique recipients of dispensed drug. Declines exceeded those observed for other prescription opioids in aggregate. After its introduction, the street price of reformulated ERO was significantly lower than original ERO. This article indicates that the abuse, therapeutic errors, and diversion of ERO declined following the introduction of a tamper-resistant reformulation of the product. Reformulating abused prescription opioids to include tamper-resistant properties may be an effective approach to reduce abuse of such products. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  4. Evaluation of the tamper-resistant properties of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets.

    PubMed

    Eisenhauer, Tiffani D; Matchett, Mike; Heasley, Ralph; Morton, Terri; Devarakonda, Krishna; Giuliani, Michael; Young, Jim L; Barrett, Thomas

    2016-01-01

    Abuse potential of extended-release (ER) opioid tablets increases if tampering causes rapid opioid release. To evaluate the susceptibility to tampering of biphasic immediate-release (IR)/ER oxycodone (OC)/acetaminophen (APAP) tablets compared with IR OC/APAP tablets. IR/ER OC/APAP and IR OC/APAP tablets were tested at room temperature and after heating, freezing and microwaving. Resistance to crushing was tested using manual and powered tools (e.g. spoons, mortar and pestle, blender, coffee grinder). Tampered tablets were tested for suitability for snorting, OC extraction in solvents and ease of drawing into a syringe. Dissolution of IR/ER OC/APAP in gastric fluid with and without ethanol was tested to determine the potential for facilitating precipitous release of opioid from the tablet. IR/ER OC/APAP tablets were more crush resistant than IR OC/APAP tablets. Heating, freezing and microwaving had no effect on crush resistance of IR/ER OC/APAP tablets. Although a mortar and pestle pulverized IR/ER OC/APAP tablets, upon contact with solvent, the powder formed a thick gel judged unsuitable for absorption through the nasal mucosa and could not be drawn into a syringe. In contrast, powder from crushed IR OC/APAP tablets dissolved readily, was judged suitable for snorting, and was easily drawn into a syringe. Dissolution of IR/ER OC/APAP tablets in gastric fluid was slowed by the addition of ethanol. IR/ER OC/APAP tablets are resistant to crushing and dissolution compared with IR OC/APAP tablets. IR/ER OC/APAP tablets may have less potential for abuse involving tampering compared with IR OC/APAP tablets.

  5. Assessment of the safety and efficacy of extended-release oxycodone/acetaminophen, for 14 days postsurgery.

    PubMed

    Singla, Neil; Barrett, Thomas; Sisk, Lisa; Kostenbader, Kenneth; Young, Jim

    2014-12-01

    To investigate the safety and satisfaction of patients treated ≤ 14 days after unilateral bunionectomy with extended-release oxycodone/acetaminophen (ER OC/APAP), a biphasic (ER and immediate release) fixed-dose combination analgesic being developed for moderate to severe acute pain. This was an open-label extension (OLE) of a randomized, double-blind, placebo-controlled trial (DBRCT) of patients undergoing bunionectomy. Patients who consented to the OLE before entering the 48 hour DBRCT entered the OLE upon completing the DBRCT and during the OLE received two tablets of ER OC/APAP (15/650 mg total dose) every 12 hours for ≤ 14 days. ClinicalTrials identifier: NCT01484652. Treatment-emergent adverse events, physical examinations, vital sign measurements, and clinical laboratory testing were assessed throughout the study. Global assessments of treatment satisfaction were made at the end of the DBRCT and at each clinic visit during the OLE. A total of 146 patients consented to the OLE before entering the DBRCT and 129 completed the OLE. Tolerability of ER OC/APAP during the OLE was consistent with that of an opioid product. Adverse events occurred during the OLE in 64 patients (43.8%); the most common were gastrointestinal events including nausea (17.8%), vomiting (7.5%), and constipation (6.2%). No changes in vital signs or clinical laboratory tests were considered by the investigator to be clinically significant. At all visits during the OLE, the majority of patients were satisfied or very satisfied with their medication. Limitations include a 14 day postprocedure study duration that may be confounded with natural healing time, and lack of a placebo arm. These results show that ER OC/APAP demonstrated an expected safety and tolerability profile and good patient satisfaction in a postsurgical model of acute pain.

  6. Oxycodone and Dexamethasone for pain management after tonsillectomy: A placebo-controlled EMG assessed clinical trial

    PubMed Central

    Vaiman, Michael; Krakovski, Daniel; Haitov, Zoe

    2011-01-01

    Summary Background Surface electromyographic (sEMG) study of post-tonsillectomy swallow-evoked muscular reactions was performed in order to evaluate the efficacy and safety of oxycodone and dexamethasone in pain management after tonsillectomy. Material/Methods 90 randomly chosen operated adults were divided into three groups. Group 1 (n=30) was treated with OxyContin (Oxycodone) injections; Group 2 (n=30) was treated with Dexacort (Dexamethasone), and Group 3 (n=30) was a placebo group. Pain assessment included visual analogue scale (VAS) pain score and the EMG data like the timing, electric amplitude and graphic patterns of muscular activity during deglutition. We investigated masseter, infrahyoid and submental-submandibular muscles. Records from trapezius muscle were used for control. The results were compared with previously established normative database. The patients were tested 24 h after surgery. The sEMG data were compared with VAS pain score with regard to changes in clinical condition of the patients. Results Analgesia with oxycodone smoothed the recorded sEMG swallow peaks and increases time of deglutition. Dexamethasone normalized muscular activity in deglutition in cases with edema as detected by the EMG records. Statistically significant difference in muscle reactions was detected between the two Groups and the placebo group. Conclusions Application of oxycodone significantly reduces the postoperative pain. Application of dexamethasone after tonsillectomy is advisable because of the reduction of postoperative morbidity while the reduction of the postoperative pain is secondary to the reduction of edema. SEMG might be used as an adjunctive measure of pain behavior via assessment of muscular reactions to pain and to analgesia. PMID:21959624

  7. Oxycodone and dexamethasone for pain management after tonsillectomy: a placebo-controlled EMG assessed clinical trial.

    PubMed

    Vaiman, Michael; Krakovski, Daniel; Haitov, Zoe

    2011-10-01

    Surface electromyographic (sEMG) study of post-tonsillectomy swallow-evoked muscular reactions was performed in order to evaluate the efficacy and safety of oxycodone and dexamethasone in pain management after tonsillectomy. 90 randomly chosen operated adults were divided into three groups. Group 1 (n = 30) was treated with OxyContin (Oxycodone) injections; Group 2 (n = 30) was treated with Dexacort (Dexamethasone), and Group 3 (n = 30) was a placebo group. Pain assessment included visual analogue scale (VAS) pain score and the EMG data like the timing, electric amplitude and graphic patterns of muscular activity during deglutition. We investigated masseter, infrahyoid and submental-submandibular muscles. Records from trapezius muscle were used for control. The results were compared with previously established normative database. The patients were tested 24 h after surgery. The sEMG data were compared with VAS pain score with regard to changes in clinical condition of the patients. Analgesia with oxycodone smoothed the recorded sEMG swallow peaks and increases time of deglutition. Dexamethasone normalized muscular activity in deglutition in cases with edema as detected by the EMG records. Statistically significant difference in muscle reactions was detected between the two Groups and the placebo group. Application of oxycodone significantly reduces the postoperative pain. Application of dexamethasone after tonsillectomy is advisable because of the reduction of postoperative morbidity while the reduction of the postoperative pain is secondary to the reduction of edema. SEMG might be used as an adjunctive measure of pain behavior via assessment of muscular reactions to pain and to analgesia.

  8. Toward evidence-based prescribing at end of life: a comparative analysis of sustained-release morphine, oxycodone, and transdermal fentanyl, with pain, constipation, and caregiver interaction outcomes in hospice patients.

    PubMed

    Weschules, Douglas J; Bain, Kevin T; Reifsnyder, Joanne; McMath, Jill A; Kupperman, David E; Gallagher, Rollin M; Hauck, Walter W; Knowlton, Calvin H

    2006-01-01

    The primary goal of this investigation was to examine selected outcomes in hospice patients who are prescribed one of three sustained-release opioid preparations. The outcomes examined include: pain score, constipation severity, and ability of the patient to communicate with caregivers. This study included 12,000 terminally ill patients consecutively admitted to hospices and receiving pharmaceutical care services between the period of July 1 and December 31, 2002. We retrospectively examined prescribing patterns of sustained-release morphine, oxycodone, and transdermal fentanyl. We compared individual opioids on the aforementioned outcome markers, as well as patient gender, terminal diagnosis, and median length of stay. Patients prescribed a sustained-release opioid had similar average ratings of pain and constipation severity, regardless of the agent chosen. Patients prescribed transdermal fentanyl were reported to have more difficulty communicating with friends and family when compared with patients prescribed either morphine or oxycodone. On average, patients prescribed transdermal fentanyl had a shorter length of stay on hospice as compared with those receiving morphine or oxycodone. There was no difference in observed pain or constipation severity among patients prescribed sustained-release opioid preparations. Patients receiving fentanyl were likely to have been prescribed the medication due to advanced illness and associated dysphagia. Diminished ability to communicate with caregivers and a shorter hospice course would be consistent with this profile. Further investigation is warranted to examine the correlation between a patient's ability to interact with caregivers and pain control achieved.

  9. A single-dose, 3-way crossover pharmacokinetic comparison between immediate-release oxycodone hydrochloride with aversion technology (IRO-A, Oxecta), IRO-a with Niacin, and Oxycodone Hydrochloride (Roxicodone) in healthy adults under fasting conditions.

    PubMed

    Leibowitz, Mark T; Zamora, Cynthia A; Brzeczko, Albert W; Stark, Jeffrey G

    2014-01-01

    Snorting and intravenous use are common routes of administration for advanced opioid abusers. A tablet form of immediate-release oxycodone (IRO) developed using Aversion Technology combines immediate release (IR) oxycodone HCl with inactive functional excipients that are intended to discourage tampering associated with intranasal and intravenous abuse (IRO-A; Oxecta, Pfizer). The purpose of this single-dose, open-label, randomized, 3-period, 3-treatment crossover study was to evaluate the bioequivalence of IRO-A to the marketed immediate-release oxycodone HCl (IRO; Roxicodone, Xanodyne Pharmaceuticals Inc., Newport, KY). IRO-A was also compared with IRO-A with niacin, a product previously developed containing the same functional excipients plus niacin as an aversive agent to discourage oral overconsumption. Healthy adults (N = 40) aged 18-55 years received single 15-mg doses of IRO-A, IRO-A with niacin (60 mg), or IRO after fasting overnight. Naltrexone was administered to diminish opioid effects. Doses were separated by a ≥7-day washout. Plasma samples taken at designated time points were analyzed using liquid chromatography with tandem mass spectrometry. Geometric mean ratios for ln-transformed parameters for IRO-A and IRO were 92%, 104%, and 104% for Cmax, AUClast (AUC is area under the concentration-time curve), and AUCinf; 90% confidence intervals were within the accepted 80%-125% range. IRO-A was also bioequivalent to IRO-A with niacin. Adverse events were mild to moderate in intensity and typical of opioid therapy (nausea, headache, vomiting). Flushing only occurred when the subjects received the IRO-A with niacin treatment (9/37 subjects). The results demonstrated that IRO-A is bioequivalent to IRO and IRO-A with niacin. With features designed to discourage tampering associated with common forms of abuse, IRO-A may provide an alternative to conventional immediate-release oxycodone formulations.

  10. Oxycodone: a pharmacological and clinical review.

    PubMed

    Ordóñez Gallego, A; González Barón, M; Espinosa Arranz, E

    2007-05-01

    Oxycodone is a semi-synthetic opioid with an agonist activity on mu, kappa and delta receptors. Equivalence with regard to morphine is 1:2. Its effect commences one hour after administration and lasts for 12 h in the controlled-release formulation. Plasma halflife is 3-5 h (half that of morphine) and stable plasma levels are reached within 24 h (2-7 days for morphine). Oral bioavailability ranges from 60 to 87%, and plasma protein binding is 45%. Most of the drug is metabolised in the liver, while the rest is excreted by the kidney along with its metabolites. The two main metabolites are oxymorphone--which is also a very potent analgesic--and noroxycodone, a weak analgesic. Oxycodone metabolism is more predictable than that of morphine, and therefore titration is easier. Oxycodone has the same mechanism of action as other opioids: binding to a receptor, inhibition of adenylyl-cyclase and hyperpolarisation of neurons, and decreased excitability. These mechanisms also play a part in the onset of dependence and tolerance. The clinical efficacy of oxycodone is similar to that of morphine, with a ratio of 1/1.5-2 for the treatment of cancer pain. Long-term administration may be associated with less toxicity in comparison with morphine. In the future, both opioids could be used simultaneously at low doses to reduce toxicity. It does not appear that there are any differences between immediate and slow-release oxycodone, except their half-life is 3-4 h, and 12 h, respectively. In Spain, controlled-release oxycodone (OxyContin) is marketed as 10-, 20-, 40- or 80-mg tablets for b.i.d. administration. Tablets must be taken whole and must not be broken, chewed or crushed. There is no food interference. The initial dose is 10 mg b.i.d. for new treatments and no dose reduction is needed in the elderly or in cases of moderate hepatic or renal failure. Immediate-release oxycodone (OxyNorm) is also available in capsules and oral solution. Side effects are those common to opioids

  11. Comparison of oral oxycodone and naproxen in soft tissue injury pain control: a double-blind randomized clinical trial.

    PubMed

    Fathi, Marzieh; Zare, Mohammad Amin; Bahmani, Hamid Reza; Zehtabchi, Shahriar

    2015-09-01

    This randomized clinical trial compares the efficacy and safety of oral oxycodone (an oral opioid) with naproxen (a nonsteroidal anti-inflammatory drug) in acute pain control in patients with soft tissue injury. It also evaluates the need for additional doses of analgesics in the first 24 hours of discharge from emergency department (ED). Adult (>18 years old) patients with soft tissue injuries were enrolled in a teaching urban ED. Subjects were randomly allocated to receive a single dose of oral oxycodone (5 mg) or oral naproxen (250 mg). Pain scores and drugs' adverse effects were assessed before, 30 minutes, and 60 minutes after medication. efficacy in pain control (reduction in pain scale >2 points) and safety (rate of side effects). The need for additional pain medication after discharge was assessed by follow-up phone call 24 hours after discharge. A total of 150 patients were enrolled. Pain scores were similar in oxycodone vs naproxen groups before (6.21 ± 0.9 in vs 6.0 ± 1.0), 30 minutes (4.5 ± 1.4 vs 4.4 ± 1.2), and 60 minutes (2.5 ± 1.3 in vs 2.6 ± 1.3) after medication, respectively. Twelve (16.0%) patients in oral oxycodone group and 5 (6.6%) patients in naproxen group needed more analgesics in first 24 hours after ED discharge. Adverse effects were more common in oxycodone group (statistically significant difference). The most common adverse effects in oxycodone group were nausea, (13.3%); vomiting, (8.0%); dizziness, (5.3%); drowsiness, 3 (4.0%); and pruritis, (2.7%). Oral oxycodone is as effective as naproxen in soft tissue injury pain control but has a less favorable safety profile. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Comparison of epidural oxycodone and epidural morphine for post-caesarean section analgesia: A randomised controlled trial.

    PubMed

    Sng, Ban Leong; Kwok, Sarah Carol; Mathur, Deepak; Ithnin, Farida; Newton-Dunn, Clare; Assam, Pryseley Nkouibert; Sultana, Rehena; Sia, Alex Tiong Heng

    2016-03-01

    Epidural morphine after caesarean section may cause moderate to severe pruritus in women. Epidural oxycodone has been shown in non-obstetric trials to reduce pruritus when compared to morphine. We hypothesised that epidural oxycodone may reduce pruritus after caesarean section. A randomised controlled trial was conducted in pregnant women at term who underwent caesarean section with combined spinal-epidural technique initiated with intrathecal fentanyl 15 μg. Women received either epidural morphine 3 mg or epidural oxycodone 3 mg via the epidural catheter after delivery. The primary outcome was the incidence of pruritus at 24 h after caesarean section. The secondary outcomes were the pruritus scores, treatment for post-operative nausea and vomiting (PONV), pain scores and maternal satisfaction. One hundred women were randomised (group oxycodone O = 50, morphine M = 50). There was no difference between Group O and M in the incidence of pruritus (n [%] 28 [56%] vs. 31 [62%], P = 0.68) and the worst pruritus scores (mean [standard deviation] 2.6 (2.8) vs. 3.3 [3.1], P = 0.23), respectively. Both groups had similar pain scores at rest (2.7 [2.3] vs. 2.0 [2.7], P = 0.16) and sitting up (5.0 [2.3] vs. 4.6 [2.4], P = 0.38) at 24 h. Pruritus scores were lower at 4-8, 8-12 and 12-24 h with oxycodone, but pain scores were higher. Both groups had a similar need for treatment of PONV and maternal satisfaction with analgesia. There was no difference in the incidence of pruritus at 24 h between epidural oxycodone and morphine. However, pruritus scores were lower with oxycodone between 4 and 24 h after surgery with higher pain scores in the same period.

  13. Comparison of epidural oxycodone and epidural morphine for post-caesarean section analgesia: A randomised controlled trial

    PubMed Central

    Sng, Ban Leong; Kwok, Sarah Carol; Mathur, Deepak; Ithnin, Farida; Newton-Dunn, Clare; Assam, Pryseley Nkouibert; Sultana, Rehena; Sia, Alex Tiong Heng

    2016-01-01

    Background and Aims: Epidural morphine after caesarean section may cause moderate to severe pruritus in women. Epidural oxycodone has been shown in non-obstetric trials to reduce pruritus when compared to morphine. We hypothesised that epidural oxycodone may reduce pruritus after caesarean section. Methods: A randomised controlled trial was conducted in pregnant women at term who underwent caesarean section with combined spinal-epidural technique initiated with intrathecal fentanyl 15 μg. Women received either epidural morphine 3 mg or epidural oxycodone 3 mg via the epidural catheter after delivery. The primary outcome was the incidence of pruritus at 24 h after caesarean section. The secondary outcomes were the pruritus scores, treatment for post-operative nausea and vomiting (PONV), pain scores and maternal satisfaction. Results: One hundred women were randomised (group oxycodone O = 50, morphine M = 50). There was no difference between Group O and M in the incidence of pruritus (n [%] 28 [56%] vs. 31 [62%], P = 0.68) and the worst pruritus scores (mean [standard deviation] 2.6 (2.8) vs. 3.3 [3.1], P = 0.23), respectively. Both groups had similar pain scores at rest (2.7 [2.3] vs. 2.0 [2.7], P = 0.16) and sitting up (5.0 [2.3] vs. 4.6 [2.4], P = 0.38) at 24 h. Pruritus scores were lower at 4–8, 8–12 and 12–24 h with oxycodone, but pain scores were higher. Both groups had a similar need for treatment of PONV and maternal satisfaction with analgesia. Conclusion: There was no difference in the incidence of pruritus at 24 h between epidural oxycodone and morphine. However, pruritus scores were lower with oxycodone between 4 and 24 h after surgery with higher pain scores in the same period. PMID:27053782

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

    PubMed

    Anderson, Daniel T; Fritz, Kristina L; Muto, Joseph J

    2002-10-01

    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).

  15. Adding ultralow-dose naltrexone to oxycodone enhances and prolongs analgesia: a randomized, controlled trial of Oxytrex.

    PubMed

    Chindalore, Vishala L; Craven, Richard A; Yu, K Peony; Butera, Peter G; Burns, Lindsay H; Friedmann, Nadav

    2005-06-01

    Oxytrex is a novel drug that combines oxycodone with ultralow-dose naltrexone, an opioid antagonist. Ultralow-dose opioid antagonists have been demonstrated to enhance and prolong opiate analgesia and alleviate opioid tolerance and withdrawal in rodents. This 3-week, Phase II clinical trial assessed safety and analgesic efficacy of Oxytrex in patients with moderate to severe pain from osteoarthritis. Patients with a pain score > or =5 received placebo, oxycodone 4 times a day (qid), Oxytrex qid, or Oxytrex twice a day (bid). All active treatment groups received the same total daily dose and dose escalation of oxycodone starting at 10 and ending at 40 mg/day. Importantly, the Oxytrex bid group received a lower daily dose of naltrexone than Oxytrex qid (0.002 vs 0.004 mg/day). Oxytrex bid produced a 39% reduction in pain intensity, which was significantly greater than that of placebo (P < .001), oxycodone qid (P = .006), and Oxytrex qid (P = .003). Oxytrex bid was also superior to placebo in quality of analgesia (P = .002), duration of pain control each day (P = .05), patients' global assessments (P = .04), and the Western Ontario and MacMaster Universities Osteoarthritis Index total score (P = .03). The incidence of side effects was comparable between active treatments. In this Phase II dose-ranging study, Oxytrex bid demonstrated greater pain relief with a more convenient dosing schedule compared to oxycodone qid. Preclinical data have shown ultralow-dose opioid antagonists to enhance and prolong opioid analgesia while reducing analgesic tolerance and physical dependence. Recent molecular pharmacology data show a mechanism of action to be the prevention of aberrant G protein coupling by opioid receptors that underlies opioid tolerance and dependence.

  16. A Randomized Clinical Trial of Nefopam versus Ketorolac Combined With Oxycodone in Patient-Controlled Analgesia after Gynecologic Surgery.

    PubMed

    Hwang, Boo-Young; Kwon, Jae-Young; Lee, Do-Won; Kim, Eunsoo; Kim, Tae-Kyun; Kim, Hae-Kyu

    2015-01-01

    Nefopam is a centrally-acting non-opioid analgesic, which has no effect on bleeding time and platelet aggregation. There has been no study about nefopam and oxycodone combination for postoperative analgesia. In this study, we present efficacy and side effects of nefopam/oxycodone compared with ketorolac/oxycodone in patient-controlled analgesia (PCA) after gynecologic surgery. 120 patients undergoing gynecologic surgery were divided randomly into two groups: Nefopam group treated with oxycodone 1 mg and nefopam 1 mg bolus; and Ketorolac group treated with oxycodone 1 mg and ketorolac 1.5 mg bolus. After the operation, a blinded observer assessed the pain with a numeric rating scale (NRS), infused PCA dose and sedation score at 1, 4, 24, and 48 h, nausea, vomiting, headache, shivering, pruritus and delirium at 6, 24 and 48 h, and satisfaction at 48 h after the operation. Nefopam group showed less nausea than Ketorolac group within 6 h after the operation. There were no significant differences in demographic data and other complications between both groups. At 48 h after operation, satisfaction and the infused PCA volumes of Nefopam group (34.0± 19.7 ml) showed no significant differences compared to Ketorolac group (30.7± 18.4 ml, P-value= 0.46). Nefopam showed a similar efficacy and lower incidence of nausea within 6 h after the operation to that of ketorolac in PCA. Nefopam may be a useful analgesic drug for the opioid-based PCA after gynecologic surgery. Further evaluation of accurate equivalent dose of nefopam as well as pharmacokinetics of bolus administration is required.

  17. A Randomized Clinical Trial of Nefopam versus Ketorolac Combined With Oxycodone in Patient-Controlled Analgesia after Gynecologic Surgery

    PubMed Central

    Hwang, Boo-Young; Kwon, Jae-Young; Lee, Do-Won; Kim, Eunsoo; Kim, Tae-Kyun; Kim, Hae-Kyu

    2015-01-01

    Objectives: Nefopam is a centrally-acting non-opioid analgesic, which has no effect on bleeding time and platelet aggregation. There has been no study about nefopam and oxycodone combination for postoperative analgesia. In this study, we present efficacy and side effects of nefopam/oxycodone compared with ketorolac/oxycodone in patient-controlled analgesia (PCA) after gynecologic surgery. Methods: 120 patients undergoing gynecologic surgery were divided randomly into two groups: Nefopam group treated with oxycodone 1 mg and nefopam 1 mg bolus; and Ketorolac group treated with oxycodone 1 mg and ketorolac 1.5 mg bolus. After the operation, a blinded observer assessed the pain with a numeric rating scale (NRS), infused PCA dose and sedation score at 1, 4, 24, and 48 h, nausea, vomiting, headache, shivering, pruritus and delirium at 6, 24 and 48 h, and satisfaction at 48 h after the operation. Results: Nefopam group showed less nausea than Ketorolac group within 6 h after the operation. There were no significant differences in demographic data and other complications between both groups. At 48 h after operation, satisfaction and the infused PCA volumes of Nefopam group (34.0± 19.7 ml) showed no significant differences compared to Ketorolac group (30.7± 18.4 ml, P-value= 0.46). Conclusion: Nefopam showed a similar efficacy and lower incidence of nausea within 6 h after the operation to that of ketorolac in PCA. Nefopam may be a useful analgesic drug for the opioid-based PCA after gynecologic surgery. Further evaluation of accurate equivalent dose of nefopam as well as pharmacokinetics of bolus administration is required. PMID:26283884

  18. Oxycodone/Naloxone PR: A Review in Severe Refractory Restless Legs Syndrome.

    PubMed

    Frampton, James E

    2015-06-01

    An oral, fixed-dose combination of prolonged-release (PR) oxycodone with PR naloxone (Targin(®), Targiniq(®), Targinact(®); hereafter referred to as oxycodone/naloxone PR) is approved in Europe for the second-line symptomatic treatment of patients with severe to very severe idiopathic restless legs syndrome (RLS), after failure of dopaminergic therapy. Coadministration of naloxone represents a targeted approach to counteracting opioid-induced bowel dysfunction without compromising therapeutic efficacy; because of its very low oral bioavailability, naloxone blocks the action of oxycodone at opioid receptors locally in the gut. The efficacy of oxycodone/naloxone PR in patients with severe RLS inadequately controlled by previous (mainly dopaminergic) treatment has been demonstrated in RELOXYN, a 12-week, randomized, double-blind study with a 40-week open-label extension. In this pivotal study, oxycodone/naloxone PR significantly improved RLS symptoms compared with placebo from week 2 onwards; a beneficial effect of oxycodone/naloxone PR was maintained through 1 year of treatment. Furthermore, improvements in RLS symptoms in oxycodone/naloxone PR recipients were accompanied by similarly sustained improvements in disease-specific quality of life and subjective sleep variables. Oxycodone/naloxone PR was generally well tolerated, with a treatment-related adverse event profile (e.g. gastrointestinal disorders, CNS disorders, fatigue and pruritus) that was consistent with that expected for opioid therapy. Notably, there were no confirmed cases of augmentation among oxycodone/naloxone PR recipients throughout the course of the study. Results from the well-designed RELOXYN trial have thus demonstrated the value of oxycodone/naloxone PR as a second-line therapy for severe refractory RLS; further investigation of this combination product as a first-line treatment for severe RLS is now warranted.

  19. The Potential Role of an Extended-Release, Abuse-Deterrent Oxycodone/Acetaminophen Fixed-Dose Combination Product for the Treatment of Acute Pain.

    PubMed

    Pergolizzi, Joseph V; Taylor, Robert; Raffa, Robert B

    2015-06-01

    Acute pain, prevalent as part of postoperative and traumatic pain, is often sub-optimally or inadequately treated. Fixed-dose combination analgesic products that combine a reduced amount of opioid with a nonopioid analgesic such as acetaminophen (paracetamol) in a single tablet offer potential pharmacodynamic and/or pharmacokinetic benefits, and may also result in an opioid-sparing effect. A new analgesic product (XARTEMIS™ XR, Mallinckrodt Brand Pharmaceuticals, Dublin, Ireland) combines oxycodone (7.5 mg) with acetaminophen (325 mg) in an immediate-release/extended-release (ER) formulation that is indicated for the treatment of acute pain. The ER formulation of this product provides stable serum drug concentrations that in this case lasts 12 h. Oxycodone/acetaminophen is a drug combination that offers safe and effective pain relief in a variety of acute pain syndromes such as postoperative pain. The combination formulation allows a smaller amount of oxycodone per tablet and the biphasic-layered matrix of the pill for ER may present obstacles to potential abusers. No opioid is totally abuse resistant, but the lower opioid content and tamper-resistant formulation of this product might discourage abuse. Clinicians must still be mindful of the acetaminophen part of this product in the patient's overall daily intake (in light of acetaminophen hepatotoxicity). The new product appears to provide an important new choice in the armamentarium against acute pain.

  20. The Adverse Events of Oxycodone in Cancer-Related Pain: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    PubMed

    Ma, Hu; Liu, Yuan; Huang, Lang; Zeng, Xian-Tao; Jin, Su-Han; Yue, Guo-Jun; Tian, Xu; Zhou, Jian-Guo

    2016-04-01

    The adverse events (AEs) of oxycodone in cancer-related pain were controversial, so we conducted a meta-analysis to determine it. PubMed, Embase, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, and the reference of included studies were searched to recognize pertinent studies. Relative risk (RR) with 95% confidence intervals (CIs) for all AEs were all extracted. The fixed-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were completed. We identified 11 eligible trials involving 1211 patients: 604 patients included in oxycodone group and 607 patients involved in control group. Our quantitative analysis included 8 AEs, and the pooled analyses indicated that oxycodone compared with other opioids in cancer-related pain were not significantly decreased RRs of all AEs (dizziness RR = 0.94, 95% CI: 0.69-1.30, Z = 0.35, P = 0.72; nausea RR = 0.88, 95% CI: 0.72-1.07, Z = 1.26, P = 0.21; vomiting RR = 0.89, 95% CI: 0.70-1.15, Z = 0.9, P = 0.37; sleepiness RR = 0.86, 95% CI: 0.38-1.36, Z = 0.36, P = 0.72; constipation RR = 0.98, 95% CI: 0.81-1.19, Z = 0.21, P = 0.83; anorexia RR = 0.97, 95% CI = 0.58-1.62, Z = 0.11, P = 0.91; pruritus RR = 0.76, 95% CI: 0.44-1.30, Z = 1.01, P = 0.31; dysuria RR = 0.33, 95% CI: 0.07-1.62, Z = 1.36, P = 0.1)]. The subgroup analysis shown that Ox controlled-release (CR) had less sleepiness compared with MS-contin (Mc) CR (RR = 0.47, 95% CI: 0.25-0.90, P = 0.02). The power analysis suggests that all AEs have low statistical power. The present meta-analysis detected that no statistically significant difference were found among oxycodone and other opioids in all AEs, but Ox CR may had less sleepiness compared with Mc CR when subgroup analysis were conducted.

  1. Efficacy and tolerability of oxycodone versus fentanyl for intravenous patient-controlled analgesia after gastrointestinal laparotomy: A prospective, randomized, double-blind study.

    PubMed

    Ding, Zhen; Wang, Kaiguo; Wang, Baosheng; Zhou, Naibao; Li, Hao; Yan, Bo

    2016-09-01

    It has been suggested that oxycodone is effective in relieving acute postoperative pain. The aim of this study was to investigate the efficacy and tolerability of oxycodone (O) versus fentanyl (F), and the adequate potency ratio of oxycodone and fentanyl in patients with intravenous patient-controlled analgesia after gastric laparotomy. In this double-blinded, randomized, controlled study, 60 patients undergoing elective gastric laparotomy were allocated to receive either oxycodone or fentanyl for postoperative intravenous patient-controlled analgesia (potency ratio 60:1). The patients received ketorolac 60 mg before the end of anesthesia and then continued with patient-controlled analgesia for 48 hours postsurgery. Pain severity, side effects and respiration rate were recorded 30 minutes, 3, 6, 12, 24, and 48 hours after the surgery. Cumulative opioid requirements and patient satisfaction were also measured. The median consumption more than 48 hours after operation of oxycodone was 50 mg (range: 40.0-62.4 mg) and fentanyl was 0.8 mg (range: 0.6-1.1 mg), and the percentage of patients requiring rescue medication was not statistically significant. Numeric rating scores at rest and upon movement were significantly lower in group O than in F (P < 0.05). Whereas the incidences of adverse events were similar between the groups (33.3% vs 27.6%, P = 0.64), a significant higher sedation scores were found in patients given fentanyl at 30 minutes after the surgery (P = 0.04). Oxycodone was comparable to fentanyl in the relief of postoperative pain following gastric laparotomy. Oxycodone not only provides better postoperative pain relief and less sedation, but also there was a tendency toward more side effects with oxycodone.

  2. SELF ADMINISTRATION OF OXYCODONE BY ADOLESCENT AND ADULT MICE AFFECTS STRIATAL NEUROTRANSMITTER RECEPTOR GENE EXPRESSION

    PubMed Central

    Mayer-Blackwell, B.; Schlussman, S. D.; Butelman, E. R.; Ho, A.; Ott, J.; Kreek, M. J.; Zhang, Y.

    2014-01-01

    Illicit use of prescription opioid analgesics (e.g., oxycodone) in adolescence is a pressing public health issue. Our goal was to determine whether oxycodone self administration differentially affects striatal neurotransmitter receptor gene expression in the dorsal striatum of adolescent compared to adult C57BL/6J mice. Groups of adolescent mice (4 weeks old, n= 12) and of adult mice (11 weeks old, n= 11) underwent surgery during which a catheter was implanted into their jugular veins. After recovering from surgery, mice self administered oxycodone (0.25 mg/kg/infusion) 2 h/day for 14 consecutive days or served as yoked saline controls. Mice were sacrificed within 1 h after the last self-administration session and the dorsal striatum was isolated for mRNA analysis. Gene expression was analyzed with real time PCR using a commercially available neurotransmitter receptor PCR array containing 84 genes. We found that adolescent mice self administered less oxycodone than adult mice over the 14 days. Monoamine oxidase A (Maoa) and neuropeptide Y receptor 5 mRNA levels were lower in adolescent mice than in adult mice without oxycodone exposure. Oxycodone self administration increased Maoa mRNA levels compared to controls in both age groups. There was a positive correlation of the amount of oxycodone self administered in the last session or across 14 sessions with Maoa mRNA levels. Gastrin-releasing peptide receptor mRNA showed a significant Drug × Age interaction, with point-wise significance. More genes in the dorsal striatum of adolescents (19) changed in response to oxycodone self administration compared to controls than in adult (4) mice. Overall, this study demonstrates that repeated oxycodone self administration alters neurotransmitter receptors gene expression in the dorsal striatum of adolescent and adult mice. PMID:24220688

  3. Self administration of oxycodone by adolescent and adult mice affects striatal neurotransmitter receptor gene expression.

    PubMed

    Mayer-Blackwell, B; Schlussman, S D; Butelman, E R; Ho, A; Ott, J; Kreek, M J; Zhang, Y

    2014-01-31

    Illicit use of prescription opioid analgesics (e.g., oxycodone) in adolescence is a pressing public health issue. Our goal was to determine whether oxycodone self administration differentially affects striatal neurotransmitter receptor gene expression in the dorsal striatum of adolescent compared to adult C57BL/6J mice. Groups of adolescent mice (4 weeks old, n=12) and of adult mice (11 weeks old, n=11) underwent surgery during which a catheter was implanted into their jugular veins. After recovering from surgery, mice self administered oxycodone (0.25 mg/kg/infusion) 2 h/day for 14 consecutive days or served as yoked saline controls. Mice were sacrificed within 1h after the last self-administration session and the dorsal striatum was isolated for mRNA analysis. Gene expression was analyzed with real time PCR using a commercially available neurotransmitter receptor PCR array containing 84 genes. We found that adolescent mice self administered less oxycodone than adult mice over the 14 days. Monoamine oxidase A (Maoa) and neuropeptide Y receptor 5 mRNA levels were lower in adolescent mice than in adult mice without oxycodone exposure. Oxycodone self administration increased Maoa mRNA levels compared to controls in both age groups. There was a positive correlation of the amount of oxycodone self administered in the last session or across 14 sessions with Maoa mRNA levels. Gastrin-releasing peptide receptor mRNA showed a significant Drug × Age interaction, with point-wise significance. More genes in the dorsal striatum of adolescents (19) changed in response to oxycodone self administration compared to controls than in adult (4) mice. Overall, this study demonstrates that repeated oxycodone self administration alters neurotransmitter receptors gene expression in the dorsal striatum of adolescent and adult mice.

  4. Sustained reduction of diversion and abuse after introduction of an abuse deterrent formulation of extended release oxycodone.

    PubMed

    Severtson, Stevan Geoffrey; Ellis, Matthew S; Kurtz, Steven P; Rosenblum, Andrew; Cicero, Theodore J; Parrino, Mark W; Gilbert, Michael K; Buttram, Mance E; Dasgupta, Nabarun; BucherBartelson, Becki; Green, Jody L; Dart, Richard C

    2016-11-01

    The development of abuse deterrent formulations is one strategy for reducing prescription opioid misuse and abuse. A putative abuse deterrent formulation of oxycodone extended release (OxyContin(®)) was introduced in 2010. Early reports demonstrated reduced abuse and diversion, however, an analysis of social media found 32 feasible methods to circumvent the abuse deterrent mechanism. We measured trends of diversion, abuse and street price of OxyContin to assess the durability of the initial reduction in abuse. Data from the Poison Center Program, Drug Diversion Program, Opioid Treatment Program, Survey of Key Informant Patients Program and StreetRx program of the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS(®)) System were used. The average quarterly rates of abuse and diversion for OxyContin were compared from before reformulation to the rate in second quarter 2015. Rates were adjusted for population using US Census data and drug availability. OxyContin abuse and diversion declined significantly each quarter after reformulation and persisted for 5 years. The rate of abuse of other opioid analgesics increased initially and then decreased, but to lesser extent than OxyContin. Abuse through both oral and non-oral routes of self-administration declined following the reformulation. The geometric mean difference in the street price of reformulated OxyContin was 36% lower than the reformulated product in the year after reformulation. Despite methods to circumvent the abuse deterrent mechanism, abuse and diversion of OxyContin decreased promptly following the introduction of a crush- and solubility- resistant formulation and continued to decrease over the subsequent 5 years. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  5. 77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... HUMAN SERVICES Food and Drug Administration Single-Ingredient, Immediate-Release Drug Products... AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and Drug... such products in interstate commerce. The document was published with an incorrect Web link....

  6. Effects of an Oxycodone Conjugate Vaccine on Oxycodone Self-Administration and Oxycodone-Induced Brain Gene Expression in Rats

    PubMed Central

    Pravetoni, Marco; Pentel, Paul R.; Potter, David N.; Chartoff, Elena H.; Tally, Laura; LeSage, Mark G.

    2014-01-01

    Prescription opioid abuse is an increasing public health concern in the USA. A vaccine comprising a hapten (OXY) conjugated to the carrier protein keyhole limpet hemocyanin (OXY-KLH) has been shown to attenuate the antinociceptive effects of oxycodone. Here, the vaccine's ability to prevent acquisition of intravenous (i.v.) oxycodone self-administration was studied in rats. Effects of vaccination on oxycodone-induced changes in the expression of several genes within the mesolimbic system, which are regulated by chronic opiate use, were also examined. Vaccination with OXY-KLH reduced the proportion of rats acquiring i.v. self-administration of oxycodone under a fixed ratio (FR) 3 schedule of reinforcement compared to control rats immunized with the unconjugated KLH carrier protein. Vaccination significantly reduced the mean number of infusions at FR3, total number of infusions, and total oxycodone intake during the entire protocol. Compared to oxycodone self-administering control rats immunized with the carrier alone, rats vaccinated with the OXY-KLH immunogen showed increased levels of adenylate cyclase 5 (Adcy5) and decreased levels of early growth response protein 2 (Egr2) and the early immediate gene c-Fos in the striatum. These data suggest that vaccination with OXY-KLH can attenuate the reinforcing effects of oxycodone at a clinically-relevant exposure level. Analysis of mRNA expression identified some addiction-relevant markers that may be of interest in understanding oxycodone effects or the protection provided by vaccination. PMID:25025380

  7. The impact of a reformulation of extended-release oxycodone designed to deter abuse in a sample of prescription opioid abusers.

    PubMed

    Havens, Jennifer R; Leukefeld, Carl G; DeVeaugh-Geiss, Angela M; Coplan, Paul; Chilcoat, Howard D

    2014-06-01

    Prescription opioid abuse is a significant public health concern that requires strategies to reduce its impact, including development of abuse deterrent formulations. OxyContin, an extended-release oxycodone (ERO) formulation, has been widely abused. This study assessed the effects of reformulated ERO, designed to be more difficult to manipulate for purposes of intranasal and intravenous abuse, on patterns of opioid abuse among a sample of individuals from rural Appalachia with a history of ERO abuse. Structured interviews assessing opioid abuse (past 30-day abuse and retrospectively reported abuse prior to the reformulation in August 2010) were completed by 189 individuals between December 2010 and September 2011. The past 30-day prevalence and frequency of reformulated ERO abuse through any route (33%, 1.9 days/month), snorting (5%, 0.2 days/month), and injecting (0.5%, <0.1 days/month) were low and infrequent compared to that of IR oxycodone (any route: 96%, 19.5 days/month; snorting: 70%, 10.3 days/month; injecting: 51%, 10.5 days/month) and retrospectively reported abuse of original ERO in August 2010 (any route: 74%, 13.4 days/month; snorting: 39%, 6.0 days/month; injecting: 41%, 8.6 days/month). After the reformulation, the prevalence of original ERO abuse significantly declined while abuse of reformulated ERO remained steadily low. Heroin abuse was rare in this sample. In this sample, abuse of reformulated ERO was low, and lower than abuse of original ERO retrospectively and IR oxycodone concurrently, particularly through injecting and snorting routes of administration. There was no evidence to suggest that reformulated ERO became a substitute for original ERO. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. A Comparison of Oxycodone and Alfentanil in Intravenous Patient-Controlled Analgesia with a Time-Scheduled Decremental Infusion after Laparoscopic Cholecystectomy.

    PubMed

    Kwon, Young Suk; Jang, Ji Su; Lee, Na Rea; Kim, Seong Su; Kim, Young Ki; Hwang, Byeong Mun; Kang, Seong Sik; Son, Hee Jeong; Lim, So Young

    2016-01-01

    Background. Oxycodone, a semisynthetic opioid, has been widely used for acute and chronic pain. Objectives. The aim of this study was to compare the analgesic and adverse effects of oxycodone and alfentanil on postoperative pain after laparoscopic cholecystectomy. Methods. This was a prospective, randomized, double-blind study. A total of 82 patients undergoing laparoscopic cholecystectomy were randomly assigned to receive either oxycodone or alfentanil using intravenous patient-controlled analgesia (PCA). PCA was administered as a time-scheduled decremental continuous infusion based on lean body mass for 48 hours postoperatively. Patients were assessed for pain with a visual analogue scale (VAS), the cumulative PCA dose, adverse effects, sedation level at 1, 4, 8, 16, 24, and 48 hours postoperatively, and satisfaction during the postoperative 48 hours. Results. There were no significant differences (p < 0.05) between the two groups in VAS score, cumulative PCA dose, adverse effects, sedation level at 1, 4, 8, 16, 24, and 48 hours postoperatively, and satisfaction during the postoperative 48 hours. Conclusions. Our data showed that the analgesic and adverse effects of oxycodone and alfentanil were similar. Therefore, oxycodone may be a good alternative to alfentanil for pain management using intravenous PCA after laparoscopic cholecystectomy when used at a conversion ratio of 10 : 1. This trial is registered with KCT0001962.

  9. A Comparison of Oxycodone and Alfentanil in Intravenous Patient-Controlled Analgesia with a Time-Scheduled Decremental Infusion after Laparoscopic Cholecystectomy

    PubMed Central

    Jang, Ji Su; Kim, Seong Su; Kim, Young Ki; Hwang, Byeong Mun; Kang, Seong Sik; Son, Hee Jeong

    2016-01-01

    Background. Oxycodone, a semisynthetic opioid, has been widely used for acute and chronic pain. Objectives. The aim of this study was to compare the analgesic and adverse effects of oxycodone and alfentanil on postoperative pain after laparoscopic cholecystectomy. Methods. This was a prospective, randomized, double-blind study. A total of 82 patients undergoing laparoscopic cholecystectomy were randomly assigned to receive either oxycodone or alfentanil using intravenous patient-controlled analgesia (PCA). PCA was administered as a time-scheduled decremental continuous infusion based on lean body mass for 48 hours postoperatively. Patients were assessed for pain with a visual analogue scale (VAS), the cumulative PCA dose, adverse effects, sedation level at 1, 4, 8, 16, 24, and 48 hours postoperatively, and satisfaction during the postoperative 48 hours. Results. There were no significant differences (p < 0.05) between the two groups in VAS score, cumulative PCA dose, adverse effects, sedation level at 1, 4, 8, 16, 24, and 48 hours postoperatively, and satisfaction during the postoperative 48 hours. Conclusions. Our data showed that the analgesic and adverse effects of oxycodone and alfentanil were similar. Therefore, oxycodone may be a good alternative to alfentanil for pain management using intravenous PCA after laparoscopic cholecystectomy when used at a conversion ratio of 10 : 1. This trial is registered with KCT0001962. PMID:27725791

  10. Comparison of oxycodone and sufentanil for patient-controlled intravenous analgesia after laparoscopic radical gastrectomy: A randomized double-blind clinical trial

    PubMed Central

    Wang, Na; Zhou, Honglan; Song, Xuesong; Wang, Jinguo

    2016-01-01

    Background: Sufentanil is widely used for patient-controlled intravenous analgesia (PCIA). Oxycodone has a powerful analgesic effect and mild side effects. We conducted this study to compare the efficacy of oxycodone and sufentanil for PCIA on postoperative pain after laparoscopic radical gastrectomy. Methodology: A total of fifty patients scheduled for laparoscopic radical gastrectomy were equally randomized to receive postoperative pain treatment with either oxycodone (Group O) or sufentanil (Group S) for 48 h postoperatively. PCIA was set on demand mode without loading dose or background infusion. Postoperative cumulative sufentanil or oxycodone consumption, pain intensity, sedation status, and side effects were assessed. Results: No significant differences were detected in visual analog scale score at rest and during coughing in the two groups at various time points after operation. Group S was associated with more doses delivered by PCIA than Group O. The overall satisfaction degree was higher in Group O. The incidences of side effects were comparable between the two groups. Conclusion: Oxycodone is a valuable alternative for PCIA in patients undergoing laparoscopic radical gastrectomy. PMID:27746551

  11. A randomised controlled trial of paracetamol and ibuprofen with or without codeine or oxycodone as initial analgesia for adults with moderate pain from limb injury.

    PubMed

    Graudins, Andis; Meek, Robert; Parkinson, Jacqueline; Egerton-Warburton, Diana; Meyer, Alastair

    2016-12-01

    Compare pain relief from non-opioid, codeine and oxycodone analgesic regimens in adults with moderate pain from limb injury. Double-blind, randomised, controlled, non-inferiority trial. Three regimens of six tablets, each included 2 × 500 mg paracetamol and 2 × 200 mg ibuprofen with 2 × 100 mg thiamine (non-opioid), 2 × 30 mg codeine (codeine) or 2 × 5 mg oxycodone tablets (oxycodone). difference in mean visual analogue scale (VAS) change between groups at 30 min, with a limit of inferiority of 13. Secondary outcomes included mean change in VAS rating from baseline to 30 min for each group, patient satisfaction, need for additional analgesia and adverse events. Pain ratings taken at 60 and 90 min for patients still in ED are described. Of 182 patients randomised, non-opioid, codeine and oxycodone numbers were 61, 62 and 59. Differences (95% CI) between groups at 30 min were as follows: non-opioid versus codeine -2.6 (-8.8 to 3.6); non-opioid versus oxycodone -2.7 (-9.3 to 3.9); codeine versus oxycodone 0.1 (-6.6 to 6.4). Mean VAS reductions for non-opioid, codeine and oxycodone were -13.5, -16.1 and -16.2 mm, respectively. Satisfaction with analgesia was reported by 77.6% (64.7-87.5), 81.0% (67.2-89.0) and 73.6% (59.7-84.7) and adverse events by 3.3% (0.4-11.3), 1.6% (0.4-8.7) and 16.9% (8.4-29.0), respectively. Mean VAS reductions at 60 and 90 min were as follows: -23.2 and -18.7 mm for non-opioid; -30.7 and -33.3 mm for codeine; and -26.1 and -31.7 mm for oxycodone. At 30 min, analgesic effects of non-opioid, codeine and oxycodone groups were non-inferior. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  12. Long-term efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of non-cancer chronic pain

    PubMed Central

    Sandner-Kiesling, A; Leyendecker, P; Hopp, M; Tarau, L; Lejcko, J; Meissner, W; Sevcik, P; Hakl, M; Hrib, R; Uhl, R; Dürr, H; Reimer, K

    2010-01-01

    Objective: The aim of this study was to assess safety and efficacy of fixed combination oxycodone prolonged release (PR)/naloxone PR in terms of both analgesia and improving opioid-induced bowel dysfunction (OIBD) and associated symptoms, such as opioid-induced constipation (OIC), in adults with chronic non-cancer pain. Study design: These were open-label extension studies in which patients who had previously completed a 12-week, double-blind study received oxycodone PR/naloxone PR for up to 52 weeks. The analgesia study assessed pain using the modified Brief Pain Inventory-Short Form (BPI-SF). The bowel function study assessed improvements in constipation using the Bowel Function Index (BFI). Results: At open-label baseline in the analgesia study (n = 379), mean score [± standard deviation (SD)] for the BPI-SF item ‘average pain over the last 24 h’ was 3.9 ± 1.52, and this remained low at 6 months (3.7 ± 1.59) and 12 months (3.8 ± 1.72). Mean scores for BPI-SF item ‘sleep interference’, and the BPI-SF ‘pain’ and ‘interference with activities’ subscales also remained low throughout the 52-week study. In the bowel function study (n = 258), mean BFI score (± SD) decreased from 35.6 ± 27.74 at the start of the extension study to 20.6 ± 24.01 after 12 months of treatment with oxycodone PR/naloxone PR. Pain scores also remained low and stable during this study. Adverse events in both extension phases were consistent with those associated with opioid therapy; no additional safety concerns were observed. Conclusion: Results from these two open-label extension studies demonstrate the long-term efficacy and tolerability of fixed combination oxycodone PR/naloxone PR in the treatment of chronic pain. Patients experienced clinically relevant improvements in OIBD while receiving effective analgesic therapy. PMID:20370845

  13. In vitro assessment of the potential for abuse via the intravenous route of oxycodone DETERx® microspheres.

    PubMed

    Fleming, Alison B; Scungio, Todd A; Grima, Michael P; Mayock, Stephen P

    2016-01-01

    Abuse of prescription analgesics is a well-recognized problem, with nearly 2 million people aged 12 years or older initiating nonmedical use of pain relievers in 2012. The prevalence of opioid abuse via intravenous (IV) injection has led to the development of dosage forms designed to deter abuse using different inactive ingredients and formulation strategies. This study evaluated the IV abuse potential for a novel, microsphere-encapsulated abuse-deterrent formulation of oxycodone, Xtampza™ ER (referred to as "oxycodone DETERx"). The extraction of oxycodone DETERx and two comparators, extended-release oxycodone (oxycodone ER) and immediate-release oxycodone (oxycodone IR), was evaluated in small volumes (5 and 10 mL) of water after manipulation of the dosage forms. The syringeability and injectability of these products were evaluated to determine the feasibility of using these products via IV injection. The extraction of oxycodone from oxycodone DETERx was nominal, with <12 percent extracted under any test condition. Oxycodone ER and oxycodone IR had as much as 83 and 98 percent oxycodone extracted, respectively. Injectability and syringeability analyses showed that injection of oxycodone DETERx microspheres in suspension is not feasible. In contrast, oxycodone ER and oxycodone IR suspensions were more easily drawn into and expelled from a syringe. Furthermore, injection of molten oxycodone DETERx microspheres was also shown to be ineffective. The chemical and physical properties of oxycodone DETERx provide barriers to manipulating the microspheres for the purpose of IV injection.

  14. A randomized, double-blind study of hydromorphone hydrochloride extended-release tablets versus oxycodone hydrochloride extended-release tablets for cancer pain: efficacy and safety in Japanese cancer patients (EXHEAL: a Phase III study of EXtended-release HydromorphonE for cAncer pain reLief).

    PubMed

    Inoue, Satoshi; Saito, Yoji; Tsuneto, Satoru; Aruga, Etsuko; Ide, Azusa; Kakurai, Yasuyuki

    2017-01-01

    In Japan, there are limited options for switching opioid analgesics. Hydromorphone is an opioid analgesic that is routinely used instead of morphine for cancer pain; however, it is not yet available in Japan. The aim of this study was to assess the efficacy and safety of hydromorphone (DS-7113b) extended-release tablets in opioid-naïve patients with cancer pain not relieved by non-opioid analgesics. This was a multicenter, randomized, double-blind, parallel-group trial. A double-dummy method was used for blinding. Each randomized subject received either hydromorphone extended-release tablets plus placebo oxycodone hydrochloride extended-release tablets 4 mg/day (n=88) or placebo hydromorphone extended-release tablets plus oxycodone hydrochloride extended-release tablets 10 mg/day (n=93) orally for 7 days (once-daily dosing for hydromorphone and twice-daily dosing for oxycodone). The doses were adjusted as necessary. Efficacy was evaluated by change in visual analog scale (VAS) score from baseline to completion of treatment. The between-group difference in least squares mean changes in VAS score from baseline to completion or discontinuation of treatment was -0.4 mm (95% CI -5.9 to 5 mm) by analysis of covariance where the baseline VAS score was used as a covariate. The upper limit of the 95% CI was below 10 mm, which was predefined as the noninferiority limit. This verified the noninferiority of hydromorphone tablets relative to oxycodone tablets. The incidence of adverse events was 80.7% (71 of 88) in the hydromorphone group and 83.7% (77 of 93) in the oxycodone group. The most common adverse events were nausea, vomiting, somnolence, diarrhea, and constipation, most of which are commonly observed with opioid analgesics. The efficacy and safety of hydromorphone extended-release tablets were equivalent to those of the oxycodone extended-release formulation.

  15. A Randomized, Double-Blind, Double-Dummy Study to Evaluate the Intranasal Human Abuse Potential and Pharmacokinetics of a Novel Extended-Release Abuse-Deterrent Formulation of Oxycodone

    PubMed Central

    Kopecky, Ernest A.; Smith, Michael D.; Fleming, Alison B.

    2016-01-01

    Objective. Evaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx®) (herein “DETERx”). Design. Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study. Setting. Clinical research site. Subjects. There were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods. Methods. The four phases encompassed: 1) Screening; 2) Drug Discrimination; 3) Double-blind Treatment; and 4) Follow-up. Drug Discrimination tests ensured that subjects could distinguish placebo from opioid. The four Double-blind Treatments compared DETERx—administered as either a crushed intranasal (IN) or an intact oral (PO) preparation—with immediate-release oxycodone IN (OXY-IR IN) and with an intact IN and PO placebo DETERx control. Results. For primary pharmacokinetic (PK) assessments, abuse quotient (Cmax/Tmax) was lower with DETERx IN than DETERx PO; both treatments were substantially lower than OXY-IR IN (6.24, 8.60, and 69.6 ng/mL/h, respectively). For drug liking, the primary subjective pharmacodynamic (PD) endpoint, both DETERx IN and DETERx PO produced significantly lower scores than OXY-IR IN (P ≤ 0.0001 for each); DETERx IN was less liked than DETERx PO (P ≤ 0.05), mirroring the PK relationships. Objectively assessed pupillometry corroborated the more rapid and significantly greater effect of OXY-IR IN than either DETERx IN or DETERx PO (P ≤ 0.007 for each). Overall safety profiles of DETERx and OXY-IR were comparable and both were well tolerated. Conclusions. Pharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested. PMID:26814256

  16. Analgesic efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg compared with those of oxycodone 5 mg/acetaminophen 325 mg and hydrocodone 7.5 mg/acetaminophen 500 mg in patients with moderate to severe postoperative pain: a randomized, double-blind, placebo-controlled, single-dose, parallel-group study in a dental pain model.

    PubMed

    Litkowski, Leonard J; Christensen, Steven E; Adamson, Dennis N; Van Dyke, Thomas; Han, Seung-Ho; Newman, Kenneth B

    2005-04-01

    Combination therapy has been widely used for the clinical management of acute pain. By combining 2 drugs with different mechanisms of action, such therapy provides additive analgesic effects while reducing the risk for adverse effects. This study compared the efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg with those of oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, and placebo in a dental pain model. This was a multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group, single-dose study in patients experiencing moderate to severe pain after surgical removal of > or = 2 ipsilateral impacted third molars. Patients were randomly assigned to receive oxycodone 5 mg/ibuprofen 400 mg, oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, or placebo. The primary outcome measures were total pain relief through 6 hours after dosing (TOTPAR6), sum of pain intensity differences through 6 hours (SPID6), and adverse events. Secondary efficacy measures included SPID3 and TOTPAR3, peak pain relief, peak pain intensity difference, time to onset of pain relief, time to use of rescue medication, proportion of patients reporting pain half gone, and the patient's global evaluation. Two hundred forty-nine patients (43.5% male; 87.5% white; mean age, 19.1 years; mean body weight, 153.6 pounds) were randomized to treatment as follows: 62 to oxycodone 5 mg/ibuprofen 400 mg, 61 to oxycodone 5 mg/acetaminophen 325 mg, 63 to hydrocodone 7.5 mg/acetaminophen 500 mg, and 63 to placebo. Oxycodone 5 mg/ibuprofen 400 mg provided significantly greater analgesia compared with oxycodone 5 mg/acetaminophen 325 mg, hydrocodone 7.5 mg/acetaminophen 500 mg, and placebo (mean [SD] TOTPAR6, 14.98 [5.37], 9.53 [6.77], 8.36 [6.68], and 5.05 [6.49], respectively; P < 0.001, oxycodone 5 mg/ibuprofen 400 mg vs all other treatments). SPID6 values also differed significantly for oxycodone 5 mg/ibuprofen 400 mg

  17. Successful interventions in decreasing oxycodone CR prescriptions within an underserved population.

    PubMed

    Shah, Nipa R; Haddad-Lacle, Judella; Hogan, Thanh

    2015-01-01

    To use fundamental population health and Patient Centered Medical Home guidelines to create an effective intervention that would decrease the quantity of inappropriate oxycodone controlled release (CR) prescriptions within an uninsured population. This was a prospective interventional study. Patients seen in the newly formed University of Florida Community Health and Family Medicine Department Total Care Clinic, for chronic nonmalignant pain. This clinic was designed to serve the uninsured patients of Jacksonville, FL. A structured, step-wise pain management protocol was introduced and implemented, and an improved Controlled Substance User Agreement was created and implemented. Pharmacists and primary care providers collaborated on care. The primary study outcome measures were the number of oxycodone CR prescriptions over an 8-month period. At the initiation of the program, the authors averaged over 40 oxycodone CR prescriptions per month. After 3 months, the number of prescriptions dropped to an average of 10 per month, a 75 percent decrease. More importantly, the number of oxycodone CR tablets saw a corresponding 75 percent drop from over 2,500 tablets per month to approximately 600 per month. Of course, the authors were concerned that the reduction of oxycodone CR may lead to increases in the use of other opioids. However, trends for hydrocodone/acetaminophen also showed a reduction in total usage as well as all other long-acting opioids. In addition, patient satisfaction did not change significantly, and no significant complaints from patients regarding this specific change were received. By implementing criteria for oxycodone CR prescribing in an innovative, comprehensive, and unified patient-centered practice model, the authors saw a significant decrease in the number of oxycodone CR tablets prescribed per month and also a decrease in total prescriptions per month.

  18. Reductions in reported deaths following the introduction of extended-release oxycodone (OxyContin) with an abuse-deterrent formulation†

    PubMed Central

    Sessler, Nelson E; Downing, Jerod M; Kale, Hrishikesh; Chilcoat, Howard D; Baumgartner, Todd F; Coplan, Paul M

    2014-01-01

    Purpose Abuse of opioid analgesics for their psychoactive effects is associated with a large number of fatalities. The effect of making opioid tablets harder to crush/dissolve on opioid-related fatalities has not been assessed. The objective of this study was to assess the impact of introducing extended-release oxycodone (ERO [OxyContin®]) tablets containing physicochemical barriers to crushing/dissolving (reformulated ERO) on deaths reported to the manufacturer. Methods All spontaneous adverse event reports of death in the US reported to the manufacturer between 3Q2009 and 3Q2013 involving ERO were used. The mean numbers of deaths/quarter in the 3 years after reformulated ERO introduction were compared with the year before. Changes in the slope of trends in deaths were assessed using spline regression. Comparison groups consisted of non-fatal reports involving ERO and fatality reports involving ER morphine. Results Reports of death decreased 82% (95% CI: −89, −73) from the year before to the third year after (131 to 23 deaths per year) reformulation; overdose death reports decreased 87% (95% CI: −93, −78) and overdose deaths with mention of abuse-related behavior decreased 86% (95% CI:−92, −75). In contrast, non-fatal ERO reports did not decrease post-reformulation, and reported ER morphine fatalities remained unchanged. The ratio of ERO fatalities to all oxycodone fatalities decreased from 21% to 8% in the year pre-reformulation to the second year post-reformulation. Conclusions These findings, when considered in the context of previously published studies using other surveillance systems, suggest that the abuse-deterrent characteristics of reformulated ERO have decreased the fatalities associated with its misuse/abuse. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:24916486

  19. Reductions in reported deaths following the introduction of extended-release oxycodone (OxyContin) with an abuse-deterrent formulation.

    PubMed

    Sessler, Nelson E; Downing, Jerod M; Kale, Hrishikesh; Chilcoat, Howard D; Baumgartner, Todd F; Coplan, Paul M

    2014-12-01

    Abuse of opioid analgesics for their psychoactive effects is associated with a large number of fatalities. The effect of making opioid tablets harder to crush/dissolve on opioid-related fatalities has not been assessed. The objective of this study was to assess the impact of introducing extended-release oxycodone (ERO [OxyContin(®) ]) tablets containing physicochemical barriers to crushing/dissolving (reformulated ERO) on deaths reported to the manufacturer. All spontaneous adverse event reports of death in the US reported to the manufacturer between 3Q2009 and 3Q2013 involving ERO were used. The mean numbers of deaths/quarter in the 3 years after reformulated ERO introduction were compared with the year before. Changes in the slope of trends in deaths were assessed using spline regression. Comparison groups consisted of non-fatal reports involving ERO and fatality reports involving ER morphine. Reports of death decreased 82% (95% CI: -89, -73) from the year before to the third year after (131 to 23 deaths per year) reformulation; overdose death reports decreased 87% (95% CI: -93, -78) and overdose deaths with mention of abuse-related behavior decreased 86% (95% CI:-92, -75). In contrast, non-fatal ERO reports did not decrease post-reformulation, and reported ER morphine fatalities remained unchanged. The ratio of ERO fatalities to all oxycodone fatalities decreased from 21% to 8% in the year pre-reformulation to the second year post-reformulation. These findings, when considered in the context of previously published studies using other surveillance systems, suggest that the abuse-deterrent characteristics of reformulated ERO have decreased the fatalities associated with its misuse/abuse. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

  20. Abrupt decline in oxycodone-caused mortality after implementation of Florida's Prescription Drug Monitoring Program.

    PubMed

    Delcher, Chris; Wagenaar, Alexander C; Goldberger, Bruce A; Cook, Robert L; Maldonado-Molina, Mildred M

    2015-05-01

    In Florida, oxycodone-caused deaths declined substantially in 2012. Multiple important law enforcement, pharmaceutical, policy, and public health actions occurred concurrently, including implementation of a statewide Prescription Drug Monitoring Program (PDMP). The effects of the PDMP on oxycodone-caused mortality in Florida were evaluated. A time-series, quasi-experimental research design with autoregressive integrated moving average (ARIMA) statistical models, including internal and external covariates. Data included 120 repeated monthly observations. Monthly counts of oxycodone-caused deaths, obtained from the Florida Medical Examiners Commission (MEC) was the outcome variable. Models included market-entry of tamper-resistant oxycodone HC1 controlled release tablets (OxyContin(®)), enforcement crackdowns (Operation Pill Nation), and regulation by FL House Bill 7095, measured by the monthly count of Florida pain management clinics closed. Two approaches were used to test the PDMP's hypothesized effect: (1) a binary indicator variable (0=pre-implementation, 1=post-implementation), and (2) a continuous indicator consisting of the number of PDMP queries by health care providers. Oxycodone-caused mortality abruptly declined 25% the month after implementation of Florida's PDMP (p=0.008). The effect remained after integrating other related historical events into the model. Results indicate that for a system-wide increase of one PDMP query per health care provider, oxycodone-caused deaths declined by 0.229 persons per month (p=0.002). This is the first study to demonstrate that the PDMP had a significant effect in reducing oxycodone-caused mortality in Florida. Results have implications for national efforts to address the prescription drug epidemic. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Absorption of different oral dosage forms of oxycodone in the elderly: a cross-over clinical trial in patients undergoing cystoscopy.

    PubMed

    Kokki, Merja; Välitalo, Pyry; Rasanen, Ilpo; Aaltomaa, Sirpa; Ojanperä, Ilkka; Eskelinen, Matti; Kokki, Hannu

    2012-10-01

    To characterize the pharmacokinetics (PK) of oxycodone following intravenous injection and administration of three oral dosage forms (solution, capsule, and controlled-release tablet) in elderly patients (age 76-89 years) undergoing cystoscopy. This was an open, randomized study with two sequences and two visits in 15 elderly patients. The patients were given intravenous injection (over 10 min) of 5 mg of oxycodone hydrochloride trihydrate. Oxycodone hydrochloride (5 mg in all forms) was orally administered as a solution, a capsule, and a controlled-release tablet. Venous blood samples were collected up to 17 h after oxycodone administration. Population PK parameters were calculated with NONMEM VI 2.0. For intravenous injection we calculated clearance, volume of distribution at steady state, and the half-life of elimination, and for oral dosage forms also the absolute bioavailability. Clearance of the intravenous injections was 28.9 L/h; the volume of distribution at steady state and the half-life of elimination were 186 L and 5.2 h, respectively. The absolute bioavailability of oxycodone was 59 % from oral solutions, 64 % from capsules, and 55 % from controlled-release tablets. Our results indicate that, in the elderly, the bioavailability of the three different oral dosage forms of oxycodone is fairly similar.

  2. Oxycodone combined with opioid receptor antagonists: efficacy and safety.

    PubMed

    Davis, Mellar; Goforth, Harold W; Gamier, Pam

    2013-05-01

    A mu receptor antagonist combined with oxycodone (OXY) may improve pain control, reduce physical tolerance and withdrawal, minimizing opioid-related bowel dysfunction and act as an abuse deterrent. The authors cover the use of OXY plus ultra-low-dose naltrexone for analgesia and the use of sustained-release OXY plus sustained-release naloxone to reduce the opioid bowel syndrome. The authors briefly describe the use of sustained-release OXY and naltrexone pellets as a drug abuse deterrent formulation. Combinations of ultra-low-dose naltrexone plus OXY have been in separate trials involved in patients with chronic pain from osteoarthritis and idiopathic low back pain. High attrition and marginal differences between ultra-low-dose naltrexone plus OXY and OXY led to discontinuation of development. Prolonged-release (PR) naloxone combined with PR OXY demonstrates a consistent reduction in opioid-related bowel dysfunction in multiple randomized controlled trials. However, gastrointestinal side effects, including diarrhea, were increased in several trials with the combination compared with PR OXY alone. Analgesia appeared to be maintained although non-inferiority to PR OXY is not formally established. There were flaws to trial design and safety monitoring. Naltrexone has been combined with OXY in individual pellets encased in a capsule. This combination has been reported in a Phase II trial and is presently undergoing Phase III studies. Due to the lack of efficacy the combination of altered low-dose naltrexone with oxycodone should cease in development. The combination of sustained release oxycodone plus naloxone reduces constipation with a consistent benefit. Safety has been suboptimally evaluated which is a concern. Although the drug is commercially available in several countries, ongoing safety monitoring particularly high doses would be important.

  3. Hydrocodone/oxycodone overdose

    MedlinePlus

    ... calling the national toll-free Poison Help hotline (1-800-222-1222) from anywhere in the United States. Poisonous Ingredient Hydrocodone and oxycodone belong to a class of narcotic medicines called opiates. These medicines are ...

  4. The place of oxycodone/naloxone in chronic pain management

    PubMed Central

    2013-01-01

    Opioid analgesics are usually effective in the management of severe chronic pain. However, symptoms of opioid-induced bowel dysfunction (OIBD) are common during opioid therapy. Opioid-induced bowel dysfunction is often unsuccessfully managed due to limited effectiveness and numerous adverse effects of traditional laxatives. Newer treatment possibilities directed at the pathomechanism of OIBD comprise combined prolonged-release oxycodone with prolonged-release naloxone (oxycodone/naloxone) tablets. Oxycodone/naloxone provides effective analgesia with limited impact on bowel function as oxycodone displays high oral bioavailability and naloxone act as local antagonist on opioid receptors in the gastrointestinal tract due to nearly complete inactivation in the liver. Oxycodone/naloxone is administered to opioid-naive patients with severe pain and those unsuccessfully treated with weak opioids. Oxycodone/naloxone may be also administered to patients treated with strong opioids who experience intense symptoms of OIBD. Studies conducted to date indicate that oxycodone/naloxone is an important drug in chronic pain management, prevention and treatment of OIBD. PMID:23788978

  5. Efficacy and safety profile of prolonged release oxycodone in combination with naloxone (OXN PR) in Parkinson's disease patients with chronic pain.

    PubMed

    Madeo, Graziella; Schirinzi, Tommaso; Natoli, Silvia; Pierantozzi, Mariangela; Stefani, Alessandro; Dauri, Mario; Pisani, Antonio

    2015-09-01

    Pain is a relevant and often underestimated non-motor symptom affecting the quality of life of patients with Parkinson's disease (PD). Although some pain symptoms can be effectively treated by dopaminergic medication, a correct diagnosis of the different types and distribution of pain in PD is challenging, and accordingly, its treatment remains troublesome. We evaluated the efficacy and the safety of a prolonged release oral formulation of oxycodone hydrochloride combined with naloxone hydrochloride dehydrate, in a fixed ratio of 2:1 (OXN PR). A total of 16 PD patients with history of pain with a minimum intensity of four on numerical rating scale (NRS) received low-dose OXN PR (5/2.5 mg twice daily) and were observed for a period of 8 weeks. The primary efficacy measure was the pain severity measured with NRS and Brief Pain Inventory (BPI). Secondary efficacy measured the safety profile by recording the occurrence of side effects, clinical global impression of change (CGI-C), Parkinson's disease sleep scale 2 (PDSS-2), Bowel function index (BFI). Data were collected and analyzed using descriptive statistics. Patients who completed the study (14 out of 16) reported a significant pain relief as observed by the reduction of NRS and BPI scores. No adjustment of dopaminergic therapy was required. No significant changes were observed in bowel function and constipation symptoms as measured by the BFI during the 8-week period. Similarly, no changes were observed in PDSS-2 score, whereas an improvement was recorded by CGI-C compared to baseline. Low-dose oral OXN PR was efficacious for the management of pain symptoms of patients with PD. More importantly, patients did not experience significant side effects, such as constipation or sedation. Our study provides evidence that opioids can be used to treat pain symptoms in PD patients.

  6. Randomized open-label phase II study comparing oxycodone-naloxone with oxycodone in early return of gastrointestinal function after laparoscopic colorectal surgery.

    PubMed

    Creamer, F; Balfour, A; Nimmo, S; Foo, I; Norrie, J D; Williams, L J; Fearon, K C; Paterson, H M

    2017-01-01

    Combined oral modified-release oxycodone-naloxone may reduce opioid-induced postoperative gut dysfunction. This study examined the feasibility of a randomized trial of oxycodone-naloxone within the context of enhanced recovery for laparoscopic colorectal resection. In a single-centre open-label phase II feasibility study, patients received analgesia based on either oxycodone-naloxone or oxycodone. Primary endpoints were recruitment, retention and protocol compliance. Secondary endpoints included a composite endpoint of gut function (tolerance of solid food, low nausea/vomiting score, passage of flatus or faeces). Eighty-two patients were screened and 62 randomized (76 per cent); the attrition rate was 19 per cent (12 of 62), leaving 50 patients who received the allocated intervention with 100 per cent follow-up and retention (modified intention-to-treat cohort). Protocol compliance was more than 90 per cent. Return of gut function by day 3 was similar in the two groups: 13 (48 per cent) of 27 in the oxycodone-naloxone group and 15 (65 per cent) of 23 in the control group (95 per cent c.i. for difference -10·0 to 40·7 per cent; P = 0·264). However, patients in the oxycodone-naloxone group had a shorter time to first bowel movement (mean(s.d.) 87(38) h versus 111(37) h in the control group; 95 per cent c.i. for difference 2·3 to 45·4 h, P = 0·031) and reduced total (oral plus parenteral) opioid consumption (mean(s.d.) 78(36) versus 94(56) mg respectively; 95 per cent c.i. for difference -10·2 to 42·8 mg, P = 0·222). High participation, retention and protocol compliance confirmed feasibility. Potential benefits of oxycodone-naloxone in reducing time to bowel movement and total opioid consumption could be tested in a randomized trial. Registration number: NCT02109640 (https://www.clinicaltrials.gov/). © 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.

  7. Controlled-release microchips.

    PubMed

    Sharma, Sadhana; Nijdam, A Jasper; Sinha, Piyush M; Walczak, Robbie J; Liu, Xuewu; Cheng, Mark M-C; Ferrari, Mauro

    2006-05-01

    Efficient drug delivery remains an important challenge in medicine: continuous release of therapeutic agents over extended time periods in accordance with a predetermined temporal profile; local delivery at a constant rate to the tumour microenvironment to overcome much of the systemic toxicity and to improve antitumour efficacy; improved ease of administration, and increasing patient compliance required are some of the unmet needs of the present drug delivery technology. Microfabrication technology has enabled the development of novel controlled-release microchips with capabilities not present in the current treatment modalities. In this review, the current status and future prospects of different types of controlled-release microchips are summarised and analysed with reference to microneedle-based microchips, as well as providing an in-depth focus on microreservoir-based and nanoporous microchips.

  8. Behavioral and Neurochemical Changes Induced by Oxycodone Differ Between Adolescent and Adult Mice

    PubMed Central

    Zhang, Yong; Picetti, Roberto; Butelman, Eduardo R; Schlussman, Stefan D; Ho, Ann; Kreek, Mary Jeanne

    2014-01-01

    Nonmedical use of the prescription opioid analgesic oxycodone is a major problem in the United States, particularly among adolescents and young adults. This study characterized self-administration of oxycodone by adolescent and adult mice, and how this affects striatal dopamine levels. Male C57BL/6J mice (4 or 10 weeks old) were allowed to acquire oxycodone self-administration (0.25 mg/kg per infusion) for 9 days, and then tested with varying doses of oxycodone (0, 0.125, 0.25, 0.5, and 0.75 mg/kg per infusion). On completion of the self-administration study, a guide cannula was implanted into the striatum of these mice. Six days later, microdialysis was conducted on the freely moving mouse. After collection of baseline samples, oxycodone was administered i.p. (1.25, 2.5, and 5.0 mg/kg) and samples were collected for 1 h after each dose. Adult mice self-administered significantly more oxycodone across the doses tested. After 1 week, basal striatal dopamine levels were lower in mice of both ages that had self-administered oxycodone than in yoked saline controls. Oxycodone challenge increased striatal dopamine levels in a dose-dependent manner in both age groups. Of interest, the lowest dose of oxycodone led to increased striatal dopamine levels in the mice that had self-administered oxycodone during adolescence but not those that self-administered it as adults. The lower number of infusions of oxycodone self-administered by adolescent mice, and their later increased striatal dopamine in response to the lowest dose of oxycodone (not found in adults), suggest differential sensitivity to the reinforcing and neurobiological effects of oxycodone in the younger mice. PMID:18784649

  9. Efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of moderate/severe chronic non-malignant pain: results of a prospectively designed pooled analysis of two randomised, double-blind clinical trials

    PubMed Central

    2010-01-01

    Background Two randomised 12-week, double-blind, parallel-group, multicenter studies comparing oxycodone PR/naloxone PR and oxycodone PR alone on symptoms of opioid-induced bowel dysfunction in patients with moderate/severe non-malignant pain have been conducted. Methods These studies were prospectively designed to be pooled and the primary outcome measure of the pooled data analysis was to demonstrate non-inferiority in 12-week analgesic efficacy of oxycodone PR/naloxone PR versus oxycodone PR alone. Patients with opioid-induced constipation were switched to oxycodone PR and then randomised to fixed doses of oxycodone PR/naloxone PR (n = 292) or oxycodone PR (n = 295) for 12 weeks (20-80 mg/day). Results No statistically significant differences in analgesic efficacy were observed for the two treatments (p = 0.3197; non-inferiority p < 0.0001; 95% CI -0.07, 0.23) and there was no statistically significant difference in frequency of analgesic rescue medication use. Improvements in Bowel Function Index score were observed for oxycodone PR/naloxone PR by Week 1 and at every subsequent time point (-15.1; p < 0.0001; 95% CI -17.3, -13.0). AE incidence was similar for both groups (61.0% and 57.3% of patients with oxycodone PR/naloxone PR and oxycodone PR alone, respectively). Conclusions Results of this pooled analysis confirm that oxycodone PR/naloxone PR provides effective analgesia and suggest that oxycodone PR/naloxone PR improves bowel function without compromising analgesic efficacy. Trial registration numbers ClinicalTrials.gov identifier: NCT00412100 and NCT00412152 PMID:20920236

  10. A new therapeutic option for postoperative pain management with oxycodone HCI injection

    PubMed Central

    2016-01-01

    Fentanyl is the most commonly used opioid analgesic in intravenous patient-controlled analgesia (IV PCA) in Korea. IV oxycodone was approved for postoperative IV PCA by the Ministry of Food and Drug Safety of Korea in 2013. The approved dosage regimen for postoperative pain relief with IV oxycodone is IV bolus loading of 2 mg followed by PCA composed of demand boluses of 1 mg and no background infusion with an oxycodone concentration of 1 mg/ml. However, a simulation study indicated that the minimum effective analgesic concentration (MEAC, as indicated by relief of pain by administering rescue analgesics) of oxycodone was reached most quickly with a higher loading dose of 0.1 mg/kg and IV PCA with background infusion. Oxycodone is a therapeutic option as an analgesic for postoperative pain management. It is necessary to reduce the analgesic dose of oxycodone in elderly patients because metabolic clearance decreases with age. PMID:27274364

  11. Long-term evaluation of combined prolonged-release oxycodone and naloxone in patients with moderate-to-severe chronic pain: pooled analysis of extension phases of two Phase III trials

    PubMed Central

    Blagden, M; Hafer, J; Duerr, H; Hopp, M; Bosse, B

    2014-01-01

    Background While opioids provide effective analgesia, opioid-induced constipation (OIC) can severely impact quality of life and treatment compliance. This pooled analysis evaluated the maintenance of efficacy and safety during long-term treatment with combined oxycodone/naloxone prolonged-release tablets (OXN PR) in adults with moderate-to-severe chronic pain. Methods Patients (N = 474) received open-label OXN PR during 52-week extension phases of two studies, having completed 12-week, double-blind, randomized treatment with oxycodone prolonged-release tablets (Oxy PR) or OXN PR. Analgesia and bowel function were assessed at each study visit using ‘Average pain over last 24 h scale and Bowel Function Index (BFI), respectively. Treatment Satisfaction Questionnaire for Medication was assessed at study end only. Key Results Improvement in bowel function was particularly marked in patients who switched from Oxy PR in the double-blind phase to OXN PR during the extension phase, resulting in a clinically meaningful reduction (≥12 points) in BFI score: at the start of the extension phases, mean (SD) BFI score was 44.3 (28.13), and was 29.8 (26.36) for patients who had received OXN PR in the double-blind phase. One week later, BFI scores were similar for the two groups (26.5 [24.40] and 27.5 [25.60], respectively), as was observed throughout the following months. Fewer than 10% of patients received laxatives regularly. Mean 24-h pain scores were low and stable throughout the extension phases. No unexpected adverse events were observed. Conclusions & Inferences Pooled data demonstrate OXN PR is an effective long-term therapy for patients with chronic non-cancer pain, and can address symptoms of OIC. No new safety issues were observed which were attributable to the long-term administration of OXN PR. PMID:25346155

  12. Comparison of opioid doctor shopping for tapentadol and oxycodone: a cohort study.

    PubMed

    Cepeda, M Soledad; Fife, Daniel; Vo, Lien; Mastrogiovanni, Gregory; Yuan, Yingli

    2013-02-01

    Obtaining opioids from multiple prescribers, known as doctor shopping, is 1 example of opioid abuse and diversion. The dual mechanism of action of tapentadol could make tapentadol less likely to be abused than other opioids. The aim of this retrospective cohort study was to compare the risk of shopping behavior between tapentadol immediate release (IR) and oxycodone IR. Subjects exposed to tapentadol or oxycodone with no recent opioid use were included and followed for 1 year. The primary outcome was the proportion of subjects who developed shopping behavior defined as subjects who had opioid prescriptions written by >1 prescriber with ≥1 day of overlap filled at ≥3 pharmacies. The opioids involved in the shopping episodes were assessed. A total of 112,821 subjects were exposed to oxycodone and 42,940 to tapentadol. Shopping behavior was seen in .8% of the subjects in the oxycodone group and in .2% of the subjects in the tapentadol group, for an adjusted odds ratio of 3.5 (95% confidence interval, 2.8 to 4.4). In the oxycodone group, 28.0% of the shopping events involved exclusively oxycodone, whereas in the tapentadol group, .6% of the shopping events involved exclusively tapentadol. Results suggest that the risk of shopping behavior is substantially lower with tapentadol than with oxycodone. The risk of opioid doctor shopping, ie, obtaining opioid prescriptions from multiple prescribers, is lower with tapentadol than with oxycodone. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  13. Oxycodone N-oxide.

    PubMed

    Sonar, Vijayakumar N; Parkin, Sean; Crooks, Peter A

    2012-11-01

    The title compound, (5R,9R,13S,14S,17R)-14-hydroxy-3-methoxy-17-methyl-4,5-epoxymorphinan-6-one N-oxide, C(18)H(21)NO(5), has been prepared in a diastereomerically pure form by the reaction of oxycodone with 3-chloroperbenzoic acid and subsequent crystallization of the product from chloroform. The crystal packing shows that the molecule exhibits intramolecular O-H···O [D···A = 2.482 (2) Å] hydrogen bonding. In addition, there are weak intermolecular C-H...O interactions which, along with van der Waals forces, stabilize the structure. The new chiral center at the 17-position is demonstrated to be R.

  14. Controlled Release Applications of Organometals.

    ERIC Educational Resources Information Center

    Thayer, John S.

    1981-01-01

    Reviews two classes of controlled release organometals: (1) distributional, to distribute bioactive materials to control a certain target organism; and (2) protective, to protect surface or interior of some structure from attach by organisms. Specific examples are given including a discussion of controlled release for schistosomiasis. (SK)

  15. Controlled Release Applications of Organometals.

    ERIC Educational Resources Information Center

    Thayer, John S.

    1981-01-01

    Reviews two classes of controlled release organometals: (1) distributional, to distribute bioactive materials to control a certain target organism; and (2) protective, to protect surface or interior of some structure from attach by organisms. Specific examples are given including a discussion of controlled release for schistosomiasis. (SK)

  16. Comparison of rofecoxib and oxycodone plus acetaminophen in the treatment of acute pain: a randomized, double-blind, placebo-controlled study in patients with moderate to severe postoperative pain in the third molar extraction model.

    PubMed

    Korn, Scott; Vassil, Theodore C; Kotey, Paul N-A; Fricke, James R

    2004-05-01

    Opiates, acetaminophen, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2-selective inhibitors such as rofecoxib are used in the treatment of acute pain because of their anti-inflammatory and/or analgesic properties. Rofecoxib has demonstrated an improved gastrointestinal safety profile compared with nonselective NSAIDs. The aim of this study was to compare the analgesic efficacy and tolerability profile of rofecoxib 50 mg with those of the centrally acting, nonsalicylate, opiate/nonopiate analgesic combination oxycodone/acetominophen 5/325 in patients with pain after dental surgery. In this randomized, double-blind, placebo- and active comparator-controlled study, patients experiencing moderate to severe postoperative pain after extraction of > or =2 third molars (including > or =1 mandibular impaction) received a single oral dose of rofecoxib 50 mg, oxycodone/acetaminophen 5/325 mg, or placebo. End points included total pain relief over 6 hours (TOPAR6, the primary end point) and 4 hours (TOPAR4), patient's global assessment of treatment at 6 hours (GLOBAL6) and 24 hours (GLOBAL24), summed pain intensity difference over 6 hours (SPID6), onset of analgesic effect (time to perceptible/meaningful pain relief, using a 2-stopwatch method), peak pain relief (PEAKPR), peak pain intensity difference (PEAKPID), and duration of analgesic effect (time to use of rescue analgesia). Two hundred twelve patients (63% female, 37% male; 76% white, 24% other; mean [SD] age, 20.9 [4.4] years; age range, 16-41 years) were enrolled in the study and received a single oral dose of rofecoxib 50 mg (n = 90), oxycodone/acetaminophen 5/325 mg (n = 91), or placebo (n = 31). The analgesic effect of rofecoxib was significantly greater than that of oxycodone/acetaminophen at P < 0.001 for TOPAR6, TOPAR4, GLOBAL6, GLOBAL24, and SPID6; at P < 0.010 for PEAKPR and PEAKPID; and at P < 0.001 for median time to use of rescue analgesia. Significantly fewer patients in

  17. Effects of dextromethorphan and oxycodone on treatment of neuropathic pain in mice.

    PubMed

    Yang, Pao-Pao; Yeh, Geng-Chang; Huang, Eagle Yi-Kung; Law, Ping-Yee; Loh, Horace H; Tao, Pao-Luh

    2015-09-22

    Neuropathic pain is a very troublesome and difficult pain to treat. Although opioids are the best analgesics for cancer and surgical pain in clinic, only oxycodone among opioids shows better efficacy to alleviate neuropathic pain. However, many side effects associated with the use of oxycodone render the continued use of it in neuropathic pain treatment undesirable. Hence, we explored whether dextromethorphan (DM, a known N-methyl-D-aspartate receptor antagonist with neuroprotective properties) could potentiate the anti-allodynic effect of oxycodone and underlying mechanisms regarding to glial cells (astrocytes and microglia) activation and proinflammatory cytokines release in a spinal nerve injury (SNL) mice model. Oxycodone produced a dose-dependent anti-allodynic effect. Co-administration of DM at a dose of 10 mg/kg (i.p.) (DM10) which had no anti-allodynic effect by itself enhanced the acute oxycodone (1 mg/kg, s.c.) effect. When the chronic anti-allodynic effects were examined, co-administration of DM10 also significantly enhanced the oxycodone effect at 3 mg/kg. Furthermore, oxycodone decreased SNL-induced activation of glial cells (astrocytes and microglia) and plasma levels of proinflammatory cytokines (IL-6, IL-1β and TNF-α). Co-administration of DM10 potentiated these effects of oxycodone. The combined use of DM with oxycodone may have therapeutic potential for decreasing the effective dose of oxycodone on the treatment of neuropathic pain. Attenuation of the glial activation and proinflammatory cytokines in the spinal cord may be important mechanisms for these effects of DM.

  18. Behavioral flexibility and response selection are impaired after limited exposure to oxycodone

    PubMed Central

    Shapiro, Matthew L.

    2014-01-01

    Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. Potentially addictive drugs may impair flexible decision-making by altering brain mechanisms that compute reward expectancies, thereby facilitating maladaptive drug use. To investigate this hypothesis, we tested the effects of oxycodone exposure on rats in two complementary learning and memory tasks that engage distinct learning strategies and neural circuits. Rats were trained first in either a spatial or a body-turn discrimination on a radial maze. After initial training, rats were given oxycodone or vehicle injections in their home cages for 5 d. Reversal learning was tested 36 h after the final drug exposure. We hypothesized that if oxycodone impaired behavioral flexibility, then drug-exposed rats should learn reversals more slowly than controls. Oxycodone exposure impaired spatial reversal learning when reward contingencies changed rapidly, but not when they changed slowly. During rapid reversals, oxycodone-exposed rats required more trials to reach criterion, made more perseverative errors, and were more likely to make errors after correct responses than controls. Oxycodone impaired body-turn reversal learning in similar patterns. Limited exposure to oxycodone reduced behavioral flexibility when rats were tested in a drug-free state, suggesting that impaired decision-making is an enduring consequence of oxycodone exposure. PMID:25403457

  19. Behavioral flexibility and response selection are impaired after limited exposure to oxycodone.

    PubMed

    Seip-Cammack, Katharine M; Shapiro, Matthew L

    2014-12-01

    Behavioral flexibility allows individuals to adapt to situations in which rewards and goals change. Potentially addictive drugs may impair flexible decision-making by altering brain mechanisms that compute reward expectancies, thereby facilitating maladaptive drug use. To investigate this hypothesis, we tested the effects of oxycodone exposure on rats in two complementary learning and memory tasks that engage distinct learning strategies and neural circuits. Rats were trained first in either a spatial or a body-turn discrimination on a radial maze. After initial training, rats were given oxycodone or vehicle injections in their home cages for 5 d. Reversal learning was tested 36 h after the final drug exposure. We hypothesized that if oxycodone impaired behavioral flexibility, then drug-exposed rats should learn reversals more slowly than controls. Oxycodone exposure impaired spatial reversal learning when reward contingencies changed rapidly, but not when they changed slowly. During rapid reversals, oxycodone-exposed rats required more trials to reach criterion, made more perseverative errors, and were more likely to make errors after correct responses than controls. Oxycodone impaired body-turn reversal learning in similar patterns. Limited exposure to oxycodone reduced behavioral flexibility when rats were tested in a drug-free state, suggesting that impaired decision-making is an enduring consequence of oxycodone exposure.

  20. Birth control - slow release methods

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/007555.htm Birth control - slow release methods To use the sharing features on this page, please enable JavaScript. Certain birth control methods contain man-made forms of hormones. These ...

  1. Pharmacokinetics and bioavailability of oxycodone and acetaminophen following single-dose administration of MNK-795, a dual-layer biphasic IR/ER combination formulation, under fed and fasted conditions

    PubMed Central

    Devarakonda, Krishna; Morton, Terri; Margulis, Rachel; Giuliani, Michael; Barrett, Thomas

    2014-01-01

    Background XARTEMIS™ XR (formerly MNK-795) is a combination oxycodone (OC) and acetaminophen (APAP) analgesic with both immediate-release and extended-release (ER) components (ER OC/APAP). The tablets are designed with gastric-retentive ER oral delivery technology that releases the ER component at a controlled rate in the upper gastrointestinal tract. Because consumption of food has demonstrated an impact on the pharmacokinetics (PK) of some marketed products using gastric-retentive ER oral delivery technology, a characterization of the effects of fed (high- and low-fat diets) versus fasted conditions on the PK of ER OC/APAP was performed. Methods This Phase I study used an open-label randomized single-dose three-period six-sequence crossover single-center design. Healthy adult participants (n=48) were randomized to receive two tablets of ER OC/APAP under three conditions: following a high-fat meal; following a low-fat meal; and fasted. Plasma concentration versus time data from predose throughout designated times up to 48 hours postdose was used to estimate the PK parameters of oxycodone and APAP. Results Thirty-one participants completed all three treatment periods. Both oxycodone and APAP were rapidly absorbed under fasted conditions. Total oxycodone and APAP exposures (area under the plasma drug concentration-time curve [AUC]) from ER OC/APAP were not significantly affected by food, and minimal changes to maximum observed plasma concentration for oxycodone and APAP were also noted. However, food marginally delayed the time to maximum observed plasma concentration of oxycodone and APAP. There was no indication that tolerability was affected by food. Conclusion The findings from this study suggest that ER OC/APAP can be administered with or without food. PMID:25170252

  2. Evaluation of Patient Migration Patterns and Related Health Care Costs Within a National Medicare Advantage Prescription Drug Plan After Implementation of an Oxycodone HCl Extended-Release Access Restriction.

    PubMed

    Chen, Chi-Chang; De, Ajita P; Sweet, Brian; Wade, Rolin L

    2017-08-01

    Health plans use formulary restrictions (e.g., prior authorization, step therapy, tier change, nonformulary status) in an effort to control cost and promote quality, safety, and appropriate prescription utilization. Some Medicare payers perceive that the inclusion of certain agents, such as branded oxycodone HCl extended-release tablets (OERs), on their formularies is associated with attracting high-cost members to the plan. To evaluate disenrollment rates, patient migration, and subsequent health care costs among OER users who disenrolled from a national Medicare Advantage Prescription Drug plan (study-MAPD) in the plan year following OER nonformulary restriction. A retrospective, longitudinal cohort study using IMS pharmacy and medical claims data between July 1, 2011, and December 31, 2014, was conducted. In the study-MAPD, adults aged ≥ 18 years who were chronic OER users with ≥ 2 OER claims 6 months before the nonformulary restriction date on January 1, 2013 (index date) and with continuous activity in pharmacy and medical claims for 6 months pre- and post-index were included in the study. Comparison years of 2012 and 2014 prerestriction/postrestriction were selected. All groups were followed for 6 months postindex. Year-to-year disenrollment rates of OER patients and the overall plan, as well as patient characteristics and costs of those who disenrolled from and those who remained with the plan, were measured. Costs were compared using a difference-in-differences approach. This study identified 2,935 eligible OER users from the study-MAPD population after imposing nonformulary restrictions on OERs on January 1, 2013. Mean age was 62.1 years, and 59.8% were female. The mean Charlson Comorbidity Index score was 1.83 for those 1,001 patients with medical claims data. For comparison years 2012 (prerestriction) and 2014 (postrestriction), 2,248 and 2,222 OER patients were identified, respectively. Patient characteristics were similar across patient cohorts in

  3. Optogenetic control of ATP release

    NASA Astrophysics Data System (ADS)

    Lewis, Matthew A.; Joshi, Bipin; Gu, Ling; Feranchak, Andrew; Mohanty, Samarendra K.

    2013-03-01

    Controlled release of ATP can be used for understanding extracellular purinergic signaling. While coarse mechanical forces and hypotonic stimulation have been utilized in the past to initiate ATP release from cells, these methods are neither spatially accurate nor temporally precise. Further, these methods cannot be utilized in a highly effective cell-specific manner. To mitigate the uncertainties regarding cellular-specificity and spatio-temporal release of ATP, we herein demonstrate use of optogenetics for ATP release. ATP release in response to optogenetic stimulation was monitored by Luciferin-Luciferase assay (North American firefly, photinus pyralis) using luminometer as well as mesoscopic bioluminescence imaging. Our result demonstrates repetitive release of ATP subsequent to optogenetic stimulation. It is thus feasible that purinergic signaling can be directly detected via imaging if the stimulus can be confined to single cell or in a spatially-defined group of cells. This study opens up new avenue to interrogate the mechanisms of purinergic signaling.

  4. Controlled release from recombinant polymers.

    PubMed

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-09-28

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed.

  5. Controlled Release from Recombinant Polymers

    PubMed Central

    Price, Robert; Poursaid, Azadeh; Ghandehari, Hamidreza

    2014-01-01

    Recombinant polymers provide a high degree of molecular definition for correlating structure with function in controlled release. The wide array of amino acids available as building blocks for these materials lend many advantages including biorecognition, biodegradability, potential biocompatibility, and control over mechanical properties among other attributes. Genetic engineering and DNA manipulation techniques enable the optimization of structure for precise control over spatial and temporal release. Unlike the majority of chemical synthetic strategies used, recombinant DNA technology has allowed for the production of monodisperse polymers with specifically defined sequences. Several classes of recombinant polymers have been used for controlled drug delivery. These include, but are not limited to, elastin-like, silk-like, and silk-elastinlike proteins, as well as emerging cationic polymers for gene delivery. In this article, progress and prospects of recombinant polymers used in controlled release will be reviewed. PMID:24956486

  6. The Adverse Events of Oxycodone in Cancer-Related Pain

    PubMed Central

    Ma, Hu; Liu, Yuan; Huang, Lang; Zeng, Xian-Tao; Jin, Su-Han; Yue, Guo-Jun; Tian, Xu; Zhou, Jian-Guo

    2016-01-01

    Abstract The adverse events (AEs) of oxycodone in cancer-related pain were controversial, so we conducted a meta-analysis to determine it. PubMed, Embase, CBM, CNKI, WanFang database, The Cochrane library, Web of Science, and the reference of included studies were searched to recognize pertinent studies. Relative risk (RR) with 95% confidence intervals (CIs) for all AEs were all extracted. The fixed-effects model was used to calculate pooled RRs and 95% CIs. Power calculation was performed using macro embedded in SAS software after all syntheses were completed. We identified 11 eligible trials involving 1211 patients: 604 patients included in oxycodone group and 607 patients involved in control group. Our quantitative analysis included 8 AEs, and the pooled analyses indicated that oxycodone compared with other opioids in cancer-related pain were not significantly decreased RRs of all AEs (dizziness RR = 0.94, 95% CI: 0.69–1.30, Z = 0.35, P = 0.72; nausea RR = 0.88, 95% CI: 0.72–1.07, Z = 1.26, P = 0.21; vomiting RR = 0.89, 95% CI: 0.70–1.15, Z = 0.9, P = 0.37; sleepiness RR = 0.86, 95% CI: 0.38–1.36, Z = 0.36, P = 0.72; constipation RR = 0.98, 95% CI: 0.81–1.19, Z = 0.21, P = 0.83; anorexia RR = 0.97, 95% CI = 0.58–1.62, Z = 0.11, P = 0.91; pruritus RR = 0.76, 95% CI: 0.44–1.30, Z = 1.01, P = 0.31; dysuria RR = 0.33, 95% CI: 0.07–1.62, Z = 1.36, P = 0.1)]. The subgroup analysis shown that Ox controlled-release (CR) had less sleepiness compared with MS-contin (Mc) CR (RR = 0.47, 95% CI: 0.25–0.90, P = 0.02). The power analysis suggests that all AEs have low statistical power. The present meta-analysis detected that no statistically significant difference were found among oxycodone and other opioids in all AEs, but Ox CR may had less sleepiness compared with Mc CR when subgroup analysis were conducted. PMID:27082588

  7. Controlled release liquid dosage formulation

    DOEpatents

    Benton, Ben F.; Gardner, David L.

    1989-01-01

    A liquid dual coated dosage formulation sustained release pharmaceutic having substantial shelf life prior to ingestion is disclosed. A dual coating is applied over controlled release cores to form dosage forms and the coatings comprise fats melting at less than approximately 101.degree. F. overcoated with cellulose acetate phthalate or zein. The dual coated dosage forms are dispersed in a sugar based acidic liquid carrier such as high fructose corn syrup and display a shelf life of up to approximately at least 45 days while still retaining their release profiles following ingestion. Cellulose acetate phthalate coated dosage form cores can in addition be dispersed in aqueous liquids of pH <5.

  8. Oral Oxycodone for Acute Postoperative Pain: A Review of Clinical Trials.

    PubMed

    Cheung, Chi Wai; Ching Wong, Stanley Sau; Qiu, Qiu; Wang, Xianyu

    2017-02-01

    Opioids are the mainstay of pain management for acute postsurgical pain. Oral oxycodone is an opioid that can provide effective acute postoperative pain relief. To evaluate the use of oral oxycodone for acute postoperative pain management. This is a narrative review based on published articles searched in PubMed and Medline from 2003 to 2015 on oral oxycodone for acute postoperative pain management. Clinical trials related to the use of oral oxycodone for acute postoperative pain management were searched via PubMed and Medline from 2003 to 2015. The search terms used were "oral strong opioids," "postsurgical," "postoperative," "post-surgical," and "post-operative." Treatment interventions were compared for analgesic efficacy, rescue medication use, side effects, recovery, length of hospital stay, and patient satisfaction. There were 26 clinical trials included in the review. Oral oxycodone showed superior postoperative analgesic efficacy compared with placebo in patients undergoing laparoscopic cholecystectomy, abdominal or pelvic surgery, bunionectomy, breast surgery, and spine surgery. When compared with intravenous opioids, oral oxycodone provided better or comparable pain relief following knee arthroplasty, spine surgery, caesarean section, laparoscopic colorectal surgery, and cardiac surgery. One study of dental postsurgery pain reported inferior pain control with oral oxycodone versus rofecoxib. (withdrawn from the US market due to cardiac safety concerns). In many studies, the demand for rescue analgesia and total opioid consumption were reduced in the oxycodone treatment arm. Patients receiving oral oxycodone experienced fewer opioid-related side effects than those on other opioids, and had a similar occurrence of postoperative nausea and vomiting as patients on placebo. Furthermore, oral oxycodone did not prolong hospital stay and was associated with lower drug costs compared with epidural and intravenous analgesics. Oxycodone administered as part of a

  9. Postoperative oxycodone toxicity in a patient with chronic pain and end-stage renal disease.

    PubMed

    Tran, Bryant W; Kohan, Lynn R; Vorenkamp, Kevin E

    2015-02-15

    We present this case to review the metabolism of oxycodone and the effects of end-stage renal disease on the elimination of oxycodone and its metabolites. A 42-year-old female with end-stage renal disease who was dependent on hemodialysis presented for left hamstring posterior capsule release. She had been receiving methadone for 2 years for chronic leg pain. On postoperative day 1, the patient's medication was changed from IV hydromorphone to oral oxycodone to treat breakthrough pain. By the next day, the patient was unarousable with notable respiratory depression. She did not fully recover after urgent hemodialysis but did have full recovery after receiving an IV naloxone infusion for 22 hours. Further study of the safety of oxycodone in hemodialysis patients is warranted.

  10. Influence of Ethanol on Oxycodone-induced Respiratory Depression: A Dose-escalating Study in Young and Elderly Individuals.

    PubMed

    van der Schrier, Rutger; Roozekrans, Margot; Olofsen, Erik; Aarts, Leon; van Velzen, Monique; de Jong, Merijn; Dahan, Albert; Niesters, Marieke

    2017-03-01

    Respiratory depression is a potentially fatal complication of opioid use, which may be exacerbated by simultaneous ethanol intake. In this three-way sequential crossover dose-escalating study, the influence of coadministration of oral oxycodone and intravenous ethanol was assessed on resting ventilation, apneic events and the hypercapnic ventilatory response in healthy young and older volunteers. Twelve young (21 to 28 yr) and 12 elderly (66 to 77 yr) opioid-naive participants ingested one 20 mg oxycodone tablet combined with an intravenous infusion of 0, 0.5, or 1 g/l ethanol. Resting respiratory variables and the primary outcome, minute ventilation at isohypercapnia (end-tidal partial pressure of carbon dioxide of 55 mmHg or VE55), were obtained at regular intervals during treatment. Oxycodone reduced baseline minute ventilation by 28% (P < 0.001 vs. control). Ethanol caused a further decrease of oxycodone-induced respiratory depression by another 19% at 1 g/l ethanol plus oxycodone (P < 0.01 vs. oxycodone). Ethanol combined with oxycodone caused a significant increase in the number of apneic events measured in a 6-min window with a median (range) increase from 1 (0 to 3) at 0 g/l ethanol to 1 (0 to 11) at 1 g/l ethanol (P < 0.01). Mean (95% CI) VE55 decreased from 33.4 (27.9 to 39.0) l/min (control) to 18.6 (15.6 to 21.6) l/min (oxycodone, P < 0.01 vs. control) and to 15.7 (12.7 to 18.6) l/min (oxycodone combined with ethanol, 1 g/l; P < 0.01 vs. oxycodone). Ethanol together with oxycodone causes greater ventilatory depression than either alone, the magnitude of which is clinically relevant. Elderly participants were more affected than younger volunteers.

  11. Efficacy and tolerability of low-dose oral prolonged-release oxycodone/naloxone for chronic nononcological pain in older patients

    PubMed Central

    Guerriero, Fabio; Sgarlata, Carmelo; Marcassa, Claudio; Ricevuti, Giovanni; Rollone, Marco

    2015-01-01

    Purpose Chronic pain is highly prevalent in older adults. Increasing evidence indicates strong opioids as a valid option for chronic pain management in geriatrics. The aim of this study was to evaluate efficacy and safety of low-dose oral prolonged-release oxycodone–naloxone (OXN-PR) in patients aged ≥70 years. Methods This open-label prospective study assessed older patients naïve to strong opioids presenting with moderate-to-severe chronic pain. Patients were prescribed OXN-PR at an initial dose of 10/5 mg/day for 28 days. In case of insufficient analgesia, the initial daily dose could be increased gradually. The primary efficacy measure was change in pain intensity from baseline, assessed by a ten-point Numeric Rating Scale (NRS) at day 28 (T28). Changes in cognitive state, daily functioning, quality of life, constipation, and other adverse events were assessed. Results Of 53 patients enrolled (mean 81.7±6.2 years [range 70–92 years]), 52 (98.1%) completed the 28-day observation. At T28, the primary end point (≥30% reduction in mean pain from baseline in the absence of bowel function deterioration) was achieved in 38 patients (71.7%). OXN-PR significantly relieved pain (NRS score –3.26; P<0.0001), as well as daily need for rescue paracetamol (from 86.8% at baseline to 40.4% at T28; P<0.001), and reduced impact of pain on daily activities (Brief Pain Inventory Short Form from 6.2±1.5 to 3.4±2.1; P<0.0001). OXN-PR was also associated with significant improvement in daily functioning (Barthel Index from 53.3±14.1 to 61.3±14.3; P<0.01). No changes were observed in cognitive status and bowel function. OXN-PR was well tolerated; only one patient (1.9%) prematurely withdrew from treatment, due to drowsiness. Conclusion Findings from this open-label prospective study suggest that low-dose OXN-PR may be effective and well tolerated for treatment of moderate-to-severe chronic pain in older patients. Besides its effectiveness, these data indicate that low

  12. Reversal of oxycodone and hydrocodone tolerance by diazepam.

    PubMed

    Gonek, Maciej; Akbarali, Hamid I; Henderson, Graeme; Dewey, William L

    2017-11-01

    The Centers for Disease Control has declared opioid abuse to be an epidemic. Overdose deaths are largely assumed to be the result of excessive opioid consumption. In many of these cases, however, opioid abusers are often polydrug abusers. Benzodiazepines are one of the most commonly co-abused substances and pose a significant risk to opioid users. In 2016, the FDA required boxed warnings - the FDA's strongest warning - for prescription opioid analgesics and benzodiazepines about the serious risks associated with using these medications at the same time. The point of our studies was to evaluate the interactions between these two classes of drugs. We investigated whether diazepam adds to the depressant effects of opioids or do they alter the levels of tolerance to opioids. In the present study, we have found that the antinociceptive tolerance that developed to repeated administration of oxycodone was reversed by an acute dose of diazepam. Antinociceptive tolerance to hydrocodone was also reversed by acute injection of diazepam; however, a fourfold higher dose of diazepam was required when compared to reversal of oxycodone-induced tolerance. These doses of diazepam did not potentiate the acute antinociceptive effect of either opioid. The same dose of diazepam that reversed oxycodone antinociceptive tolerance also reversed oxycodone locomotor tolerance while having no potentiating effects. These studies show that diazepam does not potentiate the acute effect of prescription opioids but reverses the tolerance developed after chronic administration of the drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Opioid rotation in patients initiated on oxycodone or morphine: a register study

    PubMed Central

    Ericson, Lisa; Ambring, Anneli; Björholt, Ingela; Dahm, Peter

    2013-01-01

    Purpose Strong opioids are recommended for the treatment of moderate to severe pain. However, some patients do not achieve a successful treatment outcome due to intolerable adverse events and/or inadequate analgesia, thus may benefit from switching to another opioid, a procedure known as “opioid rotation.” The type of opioid at treatment initiation may influence the risk of opioid rotation and the objective of this study was to assess such rotation after treatment initiation with two alternative treatments, controlled-release (CR) oxycodone versus CR morphine in patients suffering from non-cancer pain. Method The study reported here was a real-life study based on Swedish register data: the Prescribed Drug, National Patient, and Cause of Death registers. The captured data cover the entire Swedish population treated in specialist care. A statistical analysis plan was agreed and signed before data were accessed. Results Data from 50,223 cases were included in the analyses. The risk of rotation was 19% higher in patients initiating treatment with morphine compared with oxycodone (hazard ratio 1.19; 95% confidence interval 1.11–1.27; P < 0.001), after adjusting for such baseline variables that were both significantly correlated with the outcome variable (time to rotation) and significantly different between the groups; age at index date, osteoarthritis and number of pain-related drugs. Conclusion Patients with non-cancer pain who initiated treatment with CR morphine had a higher risk of opioid rotation than patients initiated with CR oxycodone. PMID:23717049

  14. Evaluation of the usefulness of an oxycodone immunoassay in combination with a traditional opiate immunoassay for the screening of opiates in urine.

    PubMed

    Gingras, Marie; Laberge, Marie-Hélène; Lefebvre, Michel

    2010-03-01

    Oxycodone is a semisynthetic opioid analgesic largely prescribed for post-operative and chronic pain management. The introduction of a slow release formulation of oxycodone has led to its frequent abuse and to an increase in emergency cases related to oxycodone overdose. Until recently, oxycodone testing has been confined to gas chromatography-mass spectrometry (GC-MS) analysis because the widely used automated opiate immunoassays poorly react to this compound. We investigated the utility of a new oxycodone immunoassay as a screening procedure to eliminate inappropriate GC-MS testing of negative urine specimens. We analyzed 96 urine specimens using GC-MS and two immunoassays, CEDIA((R)) opiates and DRI((R)) oxycodone assays from Microgenics, on a Hitachi 917 analyzer. The GC-MS allowed us to detect codeine, hydrocodone, hydromorphone, morphine, oxycodone, and oxymorphone following enzymatic hydrolysis and derivation by acetylation. The combination of the two immunoassays gave the best performance (98% sensitivity and specificity) when considering a positive result from GC-MS for any of the opiates. Considering positive GC-MS results for oxycodone or oxymorphone only, the oxycodone immunoassay resulted in two false-positives and one false-negative (50 ng/mL cutoff). Using these immunoassays for screening before GC-MS analysis provides a reduced opiate GC-MS workload without compromising quality.

  15. Enhanced GABAergic synaptic transmission at VLPAG neurons and potent modulation by oxycodone in a bone cancer pain model

    PubMed Central

    Takasu, Keiko; Ogawa, Koichi; Nakamura, Atsushi; Kanbara, Tomoe; Ono, Hiroko; Tomii, Takako; Morioka, Yasuhide; Hasegawa, Minoru; Shibasaki, Masahiro; Mori, Tomohisa; Suzuki, Tsutomu; Sakaguchi, Gaku

    2015-01-01

    Background and Purpose We demonstrated previously that oxycodone has potent antinociceptive effects at supraspinal sites. In this study, we investigated changes in neuronal function and antinociceptive mechanisms of oxycodone at ventrolateral periaqueductal gray (VLPAG) neurons, which are a major site of opioid action, in a femur bone cancer (FBC) model with bone cancer-related pain. Experimental Approach We characterized the supraspinal antinociceptive profiles of oxycodone and morphine on mechanical hypersensitivity in the FBC model. Based on the disinhibition mechanism underlying supraspinal opioid antinociception, the effects of oxycodone and morphine on GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) in VLPAG neurons were evaluated in slices from the FBC model. Key Results The supraspinal antinociceptive effects of oxycodone, but not morphine, were abolished by blocking G protein-gated inwardly rectifying potassium1 (Kir3.1) channels. In slices from the FBC model, GABAergic synaptic transmission at VLPAG neurons was enhanced, as indicated by a leftward shift of the input–output relationship curve of evoked IPSCs, the increased paired-pulse facilitation and the enhancement of miniature IPSC frequency. Following treatment with oxycodone and morphine, IPSCs were reduced in the FBC model, and the inhibition of presynaptic GABA release by oxycodone, but not morphine was enhanced and dependent on Kir3.1 channels. Conclusion and Implications Our results demonstrate that Kir3.1 channels are important for supraspinal antinociception and presynaptic GABA release inhibition by oxycodone in the FBC model. Enhanced GABAergic synaptic transmission at VLPAG neurons in the FBC model is an important site of supraspinal antinociception by oxycodone via Kir3.1 channel activation. PMID:25521524

  16. Patient preference with respect to QoL and reduction in opioid-induced constipation (OIC) after treatment with prolonged-release (PR) oxycodone/naloxone compared with previous analgesic therapy [PREFER study].

    PubMed

    van Dongen, V C P C; Vanelderen, P J L; Koopmans-Klein, G; van Megen, Y J B; Van Zundert, J; Huygen, F J P M

    2014-11-01

    The aim of this study was to assess patient preference in terms of quality of life (QoL), analgesia and bowel function for patients with moderate to severe chronic non-malignant pain, when treated with oxycodone PR/naloxone PR compared with the previous WHO-step I and/or WHO-step II analgesic treatment . This was a 3-week open-label phase 3b study conducted in Belgium and the Netherlands, after 3 weeks patients could enter an extension phase. Patient preference with respect to QoL for oxycodone PR/naloxone PR treatment compared with previous WHO-step I and/or WHO-step II analgesics was assessed. A patient was considered a responder with respect to QoL if this assessment was 'better' or 'much better' compared with previous WHO-step I or II analgesics at any time point. Response rate with respect to QoL was 59.2% (95% CI: 51.7-66.8%) for the Full Analysis (FA)-population, for the Per Protocol-population response rate was 71.7% (95% CI: 63.1-80.3%). Explorative analysis showed that response rate with respect to QoL was highest in constipated patients pretreated with WHO-step II analgesics (73.8%). Mean ± SD pain score in the FA-population at start was 74.7 ± 16.6 decreasing to 53.9 ± 24.3 after a median (range) treatment period of 173.5 (31-771) days. For constipated subjects the significant reduction in constipation [improvement of the Bowel Function Index (BFI)], was -24.8 points (95% CI: -17.1 to -32.5). BFI for non-constipated subjects remained well below 28.8. Adverse events with oxycodone PR/naloxone PR treatment were well-known opioid-related adverse events. This study shows that the studied patients previously treated with WHO-step I and/or WHO-step II analgesics prefer treatment with oxycodone PR/naloxone PR with respect to QoL. Moreover, the study shows that treatment with oxycodone PR/naloxone PR significantly reduces OIC in constipated patients and that non-constipated patients do not develop OIC during treatment with oxycodone PR/naloxone PR.

  17. Fixed ratio (2:1) prolonged-release oxycodone/naloxone combination improves bowel function in patients with moderate-to-severe pain and opioid-induced constipation refractory to at least two classes of laxatives.

    PubMed

    Koopmans, Gineke; Simpson, Karen; De Andrés, Javier; Lux, Eberhard Albert; Wagemans, Michel; Van Megen, Yvonne

    2014-11-01

    The effects of combined oxycodone/naloxone prolonged release tablets (OXN PR) were investigated in patients with moderate-to-severe chronic cancer-related or non-cancer pain. All patients had opioid-induced constipation (OIC) which persisted despite substantial laxative therapy. This pooled analysis included 75 patients with OIC at study entry that was refractory to at least two laxatives with different modes of action. Patients completed randomized, double-blind treatment with OXN PR 20-120 mg/day for either 12 weeks (OXN 9001: non-cancer pain study) or 4 weeks (OXN 2001: cancer-related pain study). Analgesia and bowel function were assessed using the Brief Pain Inventory Short Form and Bowel Function Index (BFI), respectively. Use of laxative medication and safety were assessed throughout the studies. NCT00513656, EudraCT 2005-002398-57, EudraCT 2005-003510-15. Statistically and clinically significant improvements in bowel function were observed following double-blind treatment with OXN PR. Mean (SD) reduction in BFI score was 21.2 (28.8) and comparable in patients with cancer-related (19.0 [28.9]) and non-cancer pain (23.3.[29.0]; P ≤ 0.0002). Furthermore, the proportion of patients with a BFI score within normal range (≤28.8) increased from 9.5% at screening to 43.1% at Day 15 of OXN PR. While all patients used ≥2 laxatives of different classes at screening, during study treatment 36% stopped using laxatives (P < 0.001). OXN PR provided effective analgesia, evidenced by stable pain scores during study treatment, and there were no unanticipated adverse events. OXN PR significantly improved bowel function and reduced the use of laxatives in patients with OIC, previously unresponsive to at least two different classes of laxatives. OXN also provided effective analgesia for patients with moderate-to-severe cancer-related pain and non-cancer-related pain.

  18. Acute Oxycodone Induces the Pro-Emetic Pica Response in RatsS⃞

    PubMed Central

    Batra, Vinita R.

    2011-01-01

    Oxycodone, a semisynthetic opioid analgesic, is frequently prescribed for the management of pain. Side effects of nausea and emesis affect patient compliance and limit its therapeutic use. The present study established that an antinociceptive dose of oxycodone (15 mg/kg; oral) induces the pica response. We found sex differences in the temporal course of pica, with females having a longer duration. Opioid receptors mediated the pica response, as 1.0 mg/kg naloxone transiently attenuated and 2.0 mg/kg naloxone blocked pica. A κ-selective antagonist failed to block the response, suggesting mediation by μ opioid receptor. For further validation, we used the well established kaolin intake model to assess pica with the chemotherapeutic drug cisplatin as a positive control. Oxycodone and cisplatin significantly increased kaolin intake 4- to 7-fold, and the wet weight of stomach was elevated 2- to 3-fold. To examine the underlying neural circuitry, we investigated c-fos activation in the area postrema and nucleus of solitary tract (NTS). Oxycodone treatment significantly increased the number of c-fos-positive neurons in the area postrema and NTS compared with water controls. As expected, cisplatin also increased the number of c-fos-positive cells in these regions. In the area postrema, the oxycodone effect was greater than cisplatin, especially at 2 h. These results indicate that an antinociceptive dose of oxycodone is associated with the expression of pica, a pro-emetic response. PMID:21875950

  19. Modelling and simulations of controlled release fertilizer

    NASA Astrophysics Data System (ADS)

    Irfan, Sayed Ameenuddin; Razali, Radzuan; Shaari, Ku Zilati Ku; Mansor, Nurlidia

    2016-11-01

    The recent advancement in controlled release fertilizer has provided an alternative solution to the conventional urea, controlled release fertilizer has a good plant nutrient uptake they are environment friendly. To have an optimum plant intake of nutrients from controlled release fertilizer it is very essential to understand the release characteristics. A mathematical model is developed to predict the release characteristics from polymer coated granule. Numerical simulations are performed by varying the parameters radius of granule, soil water content and soil porosity to study their effect on fertilizer release. Understanding these parameters helps in the better design and improve the efficiency of controlled release fertilizer.

  20. CYP2D6 Genotype Dependent Oxycodone Metabolism in Postoperative Patients

    PubMed Central

    Stamer, Ulrike M.; Zhang, Lan; Book, Malte; Lehmann, Lutz E.; Stuber, Frank; Musshoff, Frank

    2013-01-01

    Background The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption. Methods Patients received oxycodone 0.05 mg/kg before emerging from anesthesia and patient-controlled analgesia (PCA) for the subsequent 48 postoperative hours. Blood samples were drawn at 30, 90 and 180 minutes after the initial oxycodone dose. Plasma concentrations of oxycodone and its metabolites oxymorphone, noroxycodone and noroxymorphone were analyzed by liquid chromatography-mass spectrometry with electrospray ionization. CYP2D6 genotyping was performed and 121 patients were allocated to the following genotype groups: PM (poor metabolizer: no functionally active CYP2D6 allele), HZ/IM (heterozygous subjects, intermediate metabolizers with decreased CYP2D6 activity), EM (extensive metabolizers, normal CYP2D6 activity) and UM (ultrarapid metabolizers, increased CYP2D6 activity). Primary endpoint was the genotype dependent metabolite ratio of plasma concentrations oxymorphone/oxycodone. Secondary endpoint was the genotype dependent analgesic consumption with calculation of equianalgesic doses compared to the standard non-CYP dependent opioid piritramide. Results Metabolism differed between CYP2D6 genotypes. Mean (95%-CI) oxymophone/oxycodone ratios were 0.10 (0.02/0.19), 0.13 (0.11/0.16), 0.18 (0.16/0.20) and 0.28 (0.07/0.49) in PM, HZ/IM, EM and UM, respectively (p = 0.005). Oxycodone consumption up to the 12th hour was highest in PM (p = 0.005), resulting in lowest equianalgesic doses of piritramide versus oxycodone for PM (1.6 (1.4/1.8); EM and UM 2.2 (2.1/2.3); p<0.001). Pain scores did not differ between genotypes. Conclusions In this postoperative setting, the number of

  1. Cytochrome P450-mediated changes in oxycodone pharmacokinetics/pharmacodynamics and their clinical implications.

    PubMed

    Söderberg Löfdal, Karin C; Andersson, Marine L; Gustafsson, Lars L

    2013-05-01

    In recent years the use of the opioid oxycodone has increased markedly and replacing morphine as the first-line choice of opioid in several countries. There are formulations for oral immediate, oral extended release and intravenous use. The bioavailability is higher than for morphine and less variable. Oxycodone is primarily metabolized in the liver by the cytochrome P450 (CYP) enzymes with CYP3A as the major metabolic pathway and CYP2D6 as the minor metabolic pathway to noroxycodone, oxymorphone and noroxymorphone. Oxycodone exerts its analgesic effect via the µ-opioid receptor. The metabolism of CYP2D6 substrates varies to a large degree between individuals as a result of allele functionality. Poor metabolizers (PM) have two non-functional alleles, extensive metabolizers (EM) are homozygous with two functional alleles or heterozygous with one functional allele and ultrarapid metabolizers (UM) have more than two functional alleles. There are pronounced interethnic differences in the allele distribution. On the basis of studies performed thus far, oxycodone concentrations in comparison with EM are similar in PM and reduced in UM. The pharmacokinetics in UM are insufficiently investigated. Simultaneous inhibition of both CYP3A and CYP2D6 results in increased oxycodone concentrations and such a combination should be avoided. A similar effect is to be expected with use of a CYP3A inhibitor in CYP2D6 PM. Concomitant use of enzyme inducers such as rifampicin, St John's wort and carbamazepine should be avoided because of the risk of subtherapeutic concentrations of oxycodone. When the dosage of morphine may result in unpredictable bioavailability, like in patients with severe hepatic cirrhosis, oxycodone might be beneficial because it has higher and less variability in bioavailability between patients than morphine.

  2. Controlled release of subretinal fluid.

    PubMed

    Martin, B

    1975-01-01

    Drainage os subretinal fluid is generally regarded as being unnecessary when local buckling procedures are carried out, particularly when the buckle is placed radially, unless the patient has chronic glaucoma or the choroidal vessels are markedly sclerosed.However, there are many cases of retinal detachment where the eye is otherwise normal and where radial procedure is the detachment operation of choice in which a limited and controlled release of subretinal fluid will help considerably in the localisation, treatment by cryotherapy and final positioning of the tear on the buckle. This paper describes the technique employed and the advantages which may be gained by using this method in cases of deep bullous detachment of the retina. The results which have been obtained in cases in which this method has been used during the last 3 years are described.

  3. OXYCODONE COMBINATIONS FOR PAIN RELIEF

    PubMed Central

    Raffa, R.B.; Pergolizzi, J.V.; Segarnick, D.J.; Tallarida, R.J.

    2014-01-01

    SUMMARY No single analgesic drug provides the perfect therapeutic/adverse effect profile for every pain condition. In addition to convenience and possibly improved compliance, a combination of analgesic drugs offers the potential, requiring verification, of providing greater pain relief and/or reduced adverse effects than the constituent drugs when used individually. We review here analgesic combinations containing oxycodone. We found surprisingly little preclinical information about the analgesic or adverse effect profiles of the combinations (with acetaminophen, paracetamol, nonsteroidal anti-inflammatory drugs, morphine, gabapentin or pregabalin). Clinical experience and studies suggest that the combinations are safe and effective and may offer certain advantages. As with all combinations, the profile of adverse effects must also be determined in order to provide the clinician with the overall benefit/risk assessment. PMID:20571607

  4. Intranasal oxycodone self-administration in non-dependent opioid abusers

    PubMed Central

    Middleton, L.S.; Lofwall, M.R.; Nuzzo, P.A.; Siegel, A.; Walsh, S.L.

    2013-01-01

    Oxycodone, an opioid with known abuse liability, is misused by the intranasal route. Our objective was to develop a model of intranasal oxycodone self-administration useful for assessing the relative reinforcing effects of opioids and potential pharmacotherapies for opioid use disorders. Healthy, sporadic intranasal opioid abusers (n=8; 7 M, 1 F) completed this inpatient 2.5-week, randomized, double blind, placebo-controlled, crossover study. Each intranasal oxycodone dose (0, 14 & 28 mg) was tested in a separate 3-day block of sessions. The first day of each block was a sample session in which the test dose was given. Two randomized progressive ratio sessions were conducted on the next 2 days: 1) subjects could work for the test dose over 7 trials (1/7th of total dose/trial), and 2) subjects could work for either a portion of the dose (1/7th) or money ($3) over 7 trials. Physiological and subjective measures were collected before and after drug administration for all sessions. Subjects never worked to self-administer placebo regardless of whether money was available. In both self-administration sessions, oxycodone self-administration was dose-dependent. Subjects worked less for drug (28 mg oxycodone) when money was available, but only modestly so. Oxycodone dose-dependently increased VAS ratings of positive drug effects (e.g., ‘like’) during sample sessions (p<0.05). These reports were positively correlated with self-administration behavior (e.g., ‘like’, r=0.65). These data suggest that both procedures are sensitive for detecting the reinforcing properties of intranasal oxycodone and may be employed to further explore the characteristics of opioid compounds and potential pharmacotherapies for treatment. PMID:22686495

  5. The genetic influences on oxycodone response characteristics in human experimental pain.

    PubMed

    Olesen, Anne E; Sato, Hiroe; Nielsen, Lecia M; Staahl, Camilla; Droney, Joanne; Gretton, Sophy; Branford, Ruth; Drewes, Asbjørn M; Arendt-Nielsen, Lars; Riley, Julia; Ross, Joy

    2015-08-01

    Human experimental pain studies are of value to study basic pain mechanisms under controlled conditions. The aim of this study was to investigate whether genetic variation across selected mu-, kappa- and delta-opioid receptor genes (OPRM1, OPRK1and OPRD1, respectively) influenced analgesic response to oxycodone in healthy volunteers. Experimental multimodal, multitissue pain data from previously published studies carried out in Caucasian volunteers were used. Data on thermal skin pain tolerance threshold (PTT) (n = 37), muscle pressure PTT (n = 31), mechanical visceral PTT (n = 43) and thermal visceral PTT (n = 41) were included. Genetic associations with pain outcomes were explored. Nineteen opioid receptor genetic polymorphisms were included in this study. Variability in oxycodone response to skin heat was associated with OPRM1 single-nucleotide polymorphisms (SNPs) rs589046 (P < 0.0001) and rs563649 (P < 0.0001). Variability in oxycodone response to visceral pressure was associated with four OPRM1 SNPs: rs589046 (P = 0.015), rs1799971 (P = 0.045), rs9479757 (P = 0.009) and rs533586 (P = 0.046). OPRM1 SNPs were not associated with oxycodone visceral heat threshold, however, one OPRD1 rs419335 reached significance (P = 0.015). Another OPRD1 SNP rs2234918 (P = 0.041) was associated with muscle pressure. There were no associations with OPRK1 SNPs and oxycodone response for any of the pain modalities. Associations were found between analgesic effects of oxycodone and OPRM1 and OPRD1 SNPs; therefore, variation in opioid receptor genes may partly explain responder characteristics to oxycodone.

  6. Intranasal oxycodone self-administration in non-dependent opioid abusers.

    PubMed

    Middleton, Lisa S; Lofwall, Michelle R; Nuzzo, Paul A; Siegel, Anthony J; Walsh, Sharon L

    2012-08-01

    Oxycodone, an opioid with known abuse liability, is misused by the intranasal route. Our objective was to develop a model of intranasal oxycodone self-administration useful for assessing the relative reinforcing effects of opioids and potential pharmacotherapies for opioid use disorders. Healthy, sporadic intranasal opioid abusers (n = 8; 7 M, 1 F) completed this inpatient 2.5-week, randomized, double-blind, placebo-controlled, crossover study. Each intranasal oxycodone dose (0, 14 & 28 mg) was tested in a separate 3-day block of sessions. The first day of each block was a sample session in which the test dose was given. Two randomized progressive ratio sessions were conducted on the next 2 days: (1) subjects could work for the test dose over 7 trials (1/7th of total dose/trial), and (2) subjects could work for either a portion of the dose (1/7th) or money ($3) over 7 trials. Physiological and subjective measures were collected before and after drug administration for all sessions. Subjects never worked to self-administer placebo regardless of whether money was available. In both self-administration sessions, oxycodone self-administration was dose-dependent. Subjects worked less for drug (28 mg oxycodone) when money was available but only modestly so. Oxycodone dose-dependently increased VAS ratings of positive drug effects (e.g., "like") during sample sessions (p < .05). These reports were positively correlated with self-administration behavior (e.g., "like," r = .65). These data suggest that both procedures are sensitive for detecting the reinforcing properties of intranasal oxycodone and may be used to further explore the characteristics of opioid compounds and potential pharmacotherapies for treatment.

  7. Tolerability of tapentadol immediate release in patients with lower back pain or osteoarthritis of the hip or knee over 90 days: a randomized, double-blind study.

    PubMed

    Hale, Martin; Upmalis, David; Okamoto, Akiko; Lange, Claudia; Rauschkolb, Christine

    2009-05-01

    Tapentadol is a novel, centrally acting analgesic with two mechanisms of action, mu-opioid receptor agonism and norepinephrine reuptake inhibition, in a single molecule. This phase III, randomized, double-blind, active-controlled study evaluated the tolerability of tapentadol immediate release (IR) and oxycodone IR for low back pain or osteoarthritis pain (hip or knee), using flexible dosing over 90 days. Patients (N = 878) were randomly assigned (4:1 ratio) to receive tapentadol IR (50 or 100 mg, q4-6h, p.o.) or oxycodone IR (10 or 15 mg, q4-6h, p.o.). Tapentadol IR was evaluated for tolerability over 90 days, tolerability relative to oxycodone IR, withdrawal symptoms, and pain intensity. This study was not placebo-controlled, which limited efficacy evaluations. In total, 849 intent-to-treat patients received tapentadol IR (n = 679) or oxycodone IR (n = 170), and among these, 391 patients (57.6%) in the tapentadol IR group and 86 patients (50.6%) in the oxycodone IR group completed the study. Gastrointestinal events, including nausea (18.4% vs 29.4%), vomiting (16.9% vs 30.0%), and constipation (12.8% vs 27.1%), were reported by 44.2% of patients receiving tapentadol IR and 63.5% of patients receiving oxycodone IR, respectively. Nervous system events, including dizziness (18.1% vs 17.1%), headache (11.5% vs 10.0%), and somnolence (10.2% vs 9.4%), were reported by 36.7% of patients receiving tapentadol and 37.1% of patients receiving oxycodone, respectively. Odds ratios (tapentadol:oxycodone) showed that the incidences of somnolence and dizziness were similar; however, nausea, vomiting, and constipation were significantly less likely with tapentadol IR compared with oxycodone IR. The pattern of withdrawal symptoms suggests that drug tapering may not be necessary after tapentadol IR treatment of this duration. Pain intensity measurements showed similar efficacy for tapentadol and oxycodone. During this 90-day study, tapentadol IR was associated with improved

  8. Controlled Drug Release from Pharmaceutical Nanocarriers

    PubMed Central

    Lee, Jinhyun Hannah; Yeo, Yoon

    2014-01-01

    Nanocarriers providing spatiotemporal control of drug release contribute to reducing toxicity and improving therapeutic efficacy of a drug. On the other hand, nanocarriers face unique challenges in controlling drug release kinetics, due to the large surface area per volume ratio and the short diffusion distance. To develop nanocarriers with desirable release kinetics for target applications, it is important to understand the mechanisms by which a carrier retains and releases a drug, the effects of composition and morphology of the carrier on the drug release kinetics, and current techniques for preparation and modification of nanocarriers. This review provides an overview of drug release mechanisms and various nanocarriers with a specific emphasis on approaches to control the drug release kinetics. PMID:25684779

  9. Effects of repeated oxycodone administration on its analgesic and subjective effects in normal, healthy volunteers

    PubMed Central

    Cooper, Ziva D; Sullivan, Maria A; Vosburg, Suzanne K; Manubay, Jeanne M; Haney, Margaret; Foltin, Richard W; Evans, Suzette M; Kowalczyk, William J; Saccone, Phillip A; Comer, Sandra D

    2012-01-01

    Tolerance to the analgesic effects of opioids has been demonstrated in laboratory animals after repeated drug administration, yet this effect has been studied less frequently under controlled laboratory conditions in humans. This within-subject, double-blind, placebo-controlled study was designed to determine if tolerance developed to the analgesic, subjective, and physiological effects of the commonly prescribed opioid oxycodone when it was administered daily for 5 days. The effects of oxycodone’s (0, 5, and 20 mg/70 kg, p.o.) were compared, using a within-session cumulative dosing procedure, on the 1st and 5th days of the ‘daily’ dosing phase to assess for tolerance; active oxycodone was administered on the 2nd-4th days of the daily dosing phase. Changes in the effects of oxycodone were also compared when the medication was only administered on the 1st and 5th day of a 5-day ‘intermittent’ dosing phase; placebo medication was administered on the 2nd–4th days of the intermittent dosing phase. A 9-day ‘washout’ period occurred between phases when no medication was administered. Healthy volunteers (N=10) with no history of drug dependence or current drug use participated in this outpatient study. Analgesia was assessed using the Cold-Pressor Test (CPT), pain and drug effects were measured using a variety of questionnaires, and pupil diameter was monitored as an index of physiological effects. When administered daily, no differences were observed in oxycodone-induced analgesia between the 1st and 5th days, but tolerance did develop to some of the positive subjective effects of oxycodone. In contrast, oxycodone-induced analgesia and participant ratings of some positive subjective drug effects were greater on the 5th day compared to the 1st day of the intermittent dosing phase. No differences in the miotic effects of oxycodone between the 1st and 5th days of either dosing phase were detected. Though obtained under limited experimental conditions, these

  10. Synapsins Differentially Control Dopamine and Serotonin Release

    PubMed Central

    Kile, Brian M.; Guillot, Thomas S.; Venton, B. Jill; Wetsel, William C.; Augustine, George J.; Wightman, R. Mark

    2010-01-01

    Synapsins are a family of synaptic vesicle proteins that are important for neurotransmitter release. Here we have used triple knockout (TKO) mice lacking all three synapsin genes to determine the roles of synapsins in the release of two monoamine neurotransmitters, dopamine and serotonin. Serotonin release evoked by electrical stimulation was identical in substantia nigra pars reticulata slices prepared from TKO and wild-type mice. In contrast, release of dopamine in response to electrical stimulation was approximately doubled in striatum of TKO mice, both in vivo and in striatal slices, in comparison to wild-type controls. This was due to loss of synapsin III, because deletion of synapsin III alone was sufficient to increase dopamine release. Deletion of synapsins also increased the sensitivity of dopamine release to extracellular calcium ions. Although cocaine did not affect the release of serotonin from nigral tissue, this drug did enhance dopamine release. Cocaine-induced facilitation of dopamine release was a function of external calcium, an effect that was reduced in TKO mice. We conclude that synapsins play different roles in the control of release of dopamine and serotonin, with release of dopamine being negatively regulated by synapsins, specifically synapsin III, while serotonin release appears to be relatively independent of synapsins. These results provide further support for the concept that synapsin function in presynaptic terminals varies according to the neurotransmitter being released. PMID:20660258

  11. Synapsins differentially control dopamine and serotonin release.

    PubMed

    Kile, Brian M; Guillot, Thomas S; Venton, B Jill; Wetsel, William C; Augustine, George J; Wightman, R Mark

    2010-07-21

    Synapsins are a family of synaptic vesicle proteins that are important for neurotransmitter release. Here we have used triple knock-out (TKO) mice lacking all three synapsin genes to determine the roles of synapsins in the release of two monoamine neurotransmitters, dopamine and serotonin. Serotonin release evoked by electrical stimulation was identical in substantia nigra pars reticulata slices prepared from TKO and wild-type mice. In contrast, release of dopamine in response to electrical stimulation was approximately doubled in striatum of TKO mice, both in vivo and in striatal slices, in comparison to wild-type controls. This was due to loss of synapsin III, because deletion of synapsin III alone was sufficient to increase dopamine release. Deletion of synapsins also increased the sensitivity of dopamine release to extracellular calcium ions. Although cocaine did not affect the release of serotonin from nigral tissue, this drug did enhance dopamine release. Cocaine-induced facilitation of dopamine release was a function of external calcium, an effect that was reduced in TKO mice. We conclude that synapsins play different roles in the control of release of dopamine and serotonin, with release of dopamine being negatively regulated by synapsins, specifically synapsin III, while serotonin release appears to be relatively independent of synapsins. These results provide further support for the concept that synapsin function in presynaptic terminals varies according to the neurotransmitter being released.

  12. Distribution of Oxycodone in Postmortem Fluids and Tissues

    DTIC Science & Technology

    2010-06-01

    Distribution of Oxycodone in Postmortem Fluids and Tissues Sabra R. Botch Robert D. Johnson Arvind K. Chaturvedi Russell J. Lewis Civil Aerospace...Title and Subtitle 5. Report Date June 2010 6. Performing Organization Code Distribution of Oxycodone in Postmortem Fluids and Tissues 7...16. Abstract Introduction: Oxycodone is a heavily used and abused analgesic agent. Its pharmacological effects, including euphoria, respiratory

  13. Self administration of oxycodone alters synaptic plasticity gene expression in the hippocampus differentially in male adolescent and adult mice.

    PubMed

    Zhang, Y; Brownstein, A J; Buonora, M; Niikura, K; Ho, A; Correa da Rosa, J; Kreek, M J; Ott, J

    2015-01-29

    Abuse and addiction to prescription opioids such as oxycodone (a short-acting Mu opioid receptor (MOP-r) agonist) in adolescence is a pressing public health issue. We have previously shown differences in oxycodone self-administration behaviors between adolescent and adult C57BL/6J mice and expression of striatal neurotransmitter receptor genes, in areas involved in reward. In this study, we aimed to determine whether oxycodone self-administration differentially affects genes regulating synaptic plasticity in the hippocampus of adolescent compared to adult mice, since the hippocampus may be involved in learning aspects associated with chronic drug self administration. Hippocampus was isolated for mRNA analysis from mice that had self administered oxycodone (0.25 mg/kg/infusion) 2h/day for 14 consecutive days or from yoked saline controls. Gene expression was analyzed with real-time polymerase chain reaction (PCR) using a commercially available "synaptic plasticity" PCR array containing 84 genes. We found that adolescent and adult control mice significantly differed in the expression of several genes in the absence of oxycodone exposure, including those coding for mitogen-activated protein kinase, calcium/calmodulin-dependent protein kinase II gamma subunit, glutamate receptor, ionotropic AMPA2 and metabotropic 5. Chronic oxycodone self administration increased proviral integration site 1 (Pim1) and thymoma viral proto-oncogene 1 mRNA levels compared to controls in both age groups. Both Pim1 and cadherin 2 mRNAs showed a significant combined effect of Drug Condition and Age × Drug Condition. Furthermore, the mRNA levels of both cadherin 2 and cAMP response element modulators showed an experiment-wise significant difference between oxycodone and saline control in adult but not in adolescent mice. Overall, this study demonstrates for the first time that chronic oxycodone self-administration differentially alters synaptic plasticity gene expression in the hippocampus

  14. Subjective, psychomotor, and physiological effects of pregabalin alone and in combination with oxycodone in healthy volunteers.

    PubMed

    Zacny, James P; Paice, Judith A; Coalson, Dennis W

    2012-01-01

    Pregabalin is an anticonvulsant drug indicated for neuropathic disorders and fibromyalgia. Some chronic pain patients suffering from these disorders take both this drug and an opioid for pain relief. Pregabalin is a scheduled drug under the Controlled Substances Act. The subjective effects of this drug have not been well-characterized, and the extent to which it alters the subjective effects of opioids has not been studied to the best of our knowledge. Using a double-blind, randomized, crossover design, 16 healthy volunteers were administered (in separate sessions) capsules containing placebo, 75 mg pregabalin, 150 mg pregabalin, 10 mg oxycodone, and 75 mg pregabalin combined with 10 mg oxycodone. Subjective, psychomotor, and physiological measures were assessed during each of the five sessions. Pregabalin produced dose-related increases in some subjective effects and decreased respiration rate, but did not impact on psychomotor performance. Abuse liability-related subjective effects such as drug liking and desire to take the drug again were not increased by either pregabalin dose. Oxycodone produced increases in several subjective effects, including ratings of drug liking. When 75 mg pregabalin was combined with oxycodone some subjective effects were altered relative to placebo, in contrast to when each drug was tested alone. Liking of oxycodone was not increased by 75 mg pregabalin. However, recent studies have suggested that this drug is abused, and we would recommend that further psychopharmacological studies with pregabalin are warranted, including a study assessing its abuse liability across a range of doses in sedative abusers.

  15. Subjective, Psychomotor, and Physiological Effects of Pregabalin Alone and in Combination With Oxycodone in Healthy Volunteers

    PubMed Central

    Zacny, James P.; Paice, Judith A.; Coalson, Dennis W.

    2011-01-01

    Pregabalin is an anticonvulsant drug indicated for neuropathic disorders and fibromyalgia. Some chronic pain patients suffering from these disorders take both this drug and an opioid for pain relief. Pregabalin is a scheduled drug under the Controlled Substance Act. The subjective effects of this drug have not been well-characterized, and the extent to which it alters the subjective effects of opioids has not been studied to the best of our knowledge. Using a double-blind, randomized, crossover design, 16 healthy volunteers were administered (in separate sessions) capsules containing placebo, 75 mg pregabalin, 150 mg pregabalin, 10 mg oxycodone, and 75 mg pregabalin combined with 10 mg oxycodone. Subjective, psychomotor, and physiological measures were assessed during each of the five sessions. Pregabalin produced dose-related increases in some subjective effects and decreased respiration rate, but did not impact on psychomotor performance. Abuse liability-related subjective effects such as drug liking and desire to take the drug again were not increased by either pregabalin dose. Oxycodone produced increases in several subjective effects, including ratings of drug liking. When 75 mg pregabalin was combined with oxycodone some subjective effects were altered relative to placebo, in contrast to when each drug was tested alone. Liking of oxycodone was not increased by 75 mg pregabalin. However, recent studies have suggested that this drug is abused, and we would recommend that further psychopharmacological studies with pregabalin are warranted, including a study assessing its abuse liability across a range of doses in sedative abusers. PMID:22085697

  16. Intravenous oxycodone for pain relief in the first stage of labour--maternal pharmacokinetics and neonatal exposure.

    PubMed

    Kokki, Merja; Franco, Maria Gonzalez; Raatikainen, Kaisa; Välitalo, Pyry; Sankilampi, Ulla; Heinonen, Seppo; Neuvonen, Pertti J; Kokki, Hannu

    2012-09-01

    Physiological changes during pregnancy may change pharmacokinetics of compounds. Oxycodone is an increasingly used opioid agonist in acute pain management but its pharmacokinetics in labouring women has not been established. We studied the maternal pharmacokinetics and neonatal exposure of intravenous oxycodone for pain relief in the first stage of labour. The study was prospective, open-labelled and with a control group. After informed consent, 15 nulliparous parturients and newborns, and newborns in a control group were studied. In the study group, oxycodone boluses of 1 mg i.v., up to a cumulative dose of 5 mg, was administered when labour pain score was 5/10 or higher. As the control group, 30 other newborns after uncomplicated deliveries with no systemic opioids were assessed for the neonatal outcome. In the study group, maternal pharmacokinetics of oxycodone was measured from plasma concentrations during labour, and neonatal exposure was assessed from umbilical plasma samples using population pharmacokinetic methods. Maternal plasma oxycodone concentration decreased with a median half-life of 2.6 hr (range, 1.8-2.8). Oxycodone concentrations in the umbilical plasma 2.7 μg/l (0.3-14.5) were similar as in maternal plasma 2.4 (0.1-14.8) μg/l at the time of birth. No severe or unexpected adverse effects were noted. To conclude, firstly, maternal elimination half-life of i.v. oxycodone was significantly shorter than that reported in non-pregnant women, and secondly, maternal plasma oxycodone at the birth correlated well with neonatal umbilical concentrations and may, thus, be used as an estimate of neonatal exposure.

  17. Extended access oxycodone self-administration and neurotransmitter receptor gene expression in the dorsal striatum of adult C57BL/6J mice

    PubMed Central

    Zhang, Yong; Mayer-Blackwell, Brandan; Schlussman, Stefan D.; Randesi, Matthew; Butelman, Eduardo R.; Ho, Ann; Ott, Jurg; Kreek, Mary Jeanne

    2014-01-01

    Rationale Although non-medical use of oxycodone continues to be a growing problem in the United States, there are no animal studies examining the effects of long term oxycodone self administration (SA). Objectives The current study was designed to examine chronic oxycodone SA by mice (14 days), in novel extended (4 hours) SA sessions and its effect on selective striatal neurotransmitter receptor mRNA expression. Methods Adult male C57/BL6J mice were either allowed to self administer oxycodone (0.25 mg/kg/infusion, FR1) or served as yoked-saline controls in an extended access paradigm. Mice self administered oxycodone for 4 hours/day for 14 consecutive days. Comparison groups with 14-days exposure to 1-hour SA sessions were also studied. Within one hour of the last extended SA session, mice were sacrificed, dorsal striatum was isolated and selective neurotransmitter receptor mRNA levels were examined. Results The oxycodone groups poked the active hole significantly more times than the yoked controls. The number of nose pokes at the active hole rose over the 14 days in the oxycodone group with extended access. The expression of thirteen neurotransmitter receptor mRNAs was significantly altered in the dorsal striatum, including the GABA A receptor beta 2 subunit (Gabrb2) showing experiment-wise significant decrease, as a result of extended oxycodone SA. Conclusion C57BL/6J mice escalated the amount of oxycodone self administered across 14 consecutive daily extended sessions, but not 1-hour sessions. Decreases in Gabrb2 mRNA levels may underlie escalation of oxycodone intake in the extended access SA sessions. PMID:24221825

  18. Effects of cold pressor pain on the abuse liability of intranasal oxycodone in male and female prescription opioid abusers.

    PubMed

    Lofwall, Michelle R; Nuzzo, Paul A; Walsh, Sharon L

    2012-06-01

    Approximately 1.9 million persons in the U.S. have prescription opioid use disorders often with concomitant bodily pain, but systematic data on the impact of pain on abuse liability of opioids is lacking. The purpose of this study was to determine whether pain alters the intranasal abuse liability of oxycodone, a commonly prescribed and abused analgesic, in males and females. Sporadic prescription opioid abusers (10 females, 10 males) participated in this mixed (between and within-subject), randomized inpatient study. Experimental sessions (n=6) tested intranasal placebo, oxycodone 15 or 30 mg/70 kg during cold pressor testing (CPT) and a warm water control. Observer- and subject-rated drug effect measures, analgesia, physiologic and cognitive effects were assessed. The CPT significantly increased blood pressure, heart rate, pain, stress, and "opiate desire" compared to the no-pain control but did not alter opioid liking, high or street value. Intranasal oxycodone produced effects within 10 min, significantly decreasing pain and significantly increasing subjective measures of abuse liability (e.g., high). Females had higher ratings of street value, high, and liking for one or both active doses. The CPT was a reliably painful and stressful stimulus that did not diminish the abuse liability of intranasal oxycodone. Females were more sensitive to oxycodone on several abuse liability measures that warrant further follow-up. Snorting oxycodone rapidly produced psychoactive effects indicative of substantial abuse liability. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. The addiction potential of oxycodone (Percodan).

    PubMed

    BLOOMQUIST, E R

    1963-08-01

    Dihydrohydroxycodeinone (oxycodone, Percodan(R)) is a useful analgesic. Its addiction potential, however, is comparable to that of morphine. This fact should be considered when it is prescribed. Because of increasing numbers of addicts to this drug in the State of California, the California Medical Association Committee on Dangerous Drugs and the House of Delegates has recommended that oxycodone-containing drugs be returned to the triplicate prescription list as they were originally in 1949. This recommendation was incorporated in Senate Bill 385, which failed to pass the legislature.

  20. New depression diagnosis following prescription of codeine, hydrocodone or oxycodone.

    PubMed

    Scherrer, Jeffrey F; Salas, Joanne; Bucholz, Kathleen K; Schneider, F David; Burroughs, Thomas; Copeland, Laurel A; Sullivan, Mark D; Lustman, Patrick J

    2016-05-01

    Longer duration of prescription opioid use is associated with risk of major depression after controlling for daily morphine equivalent dose and pain. It is not known if risk of depression varies as a function of the type of opioid prescribed. A retrospective cohort design was used to model onset of new depression diagnosis among 11 462 Veterans Health Administration (VA) patients who were prescribed only codeine, only hydrocodone or only oxycodone for >30 days. Patients were free of prevalent opioid use and depression at baseline (2000-2001). Follow-up was 2002-2012. Propensity scores and weighting were used to balance covariates across opioid type. Cox-proportional hazard models were computed, using weighted data and additional adjustment for morphine equivalent dose (MED), duration of use, and pain after opioid initiation, to estimate the risk of new depression diagnosis among patients prescribed only codeine, only oxycodone vs. those prescribed only hydrocodone. After controlling for confounding, we observed that patients prescribed codeine, compared to hydrocodone, were significantly more likely to have a new depression diagnosis (HR = 1.27; 95%CI: 1.12-1.43). Oxycodone was significantly associated with onset of new depression diagnosis when exposure was modeled as total days exposed in post-hoc analysis, but not when exposure was duration of incident period of use. Although codeine is a less potent opioid, after controlling for MED, chronic use of this agent is associated with nearly a 30% greater risk of depression compared to hydrocodone. Additional research is needed to determine the mechanisms for this association. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Inhibition of cytochrome P450 3A by clarithromycin uniformly affects the pharmacokinetics and pharmacodynamics of oxycodone in young and elderly volunteers.

    PubMed

    Liukas, Antti; Hagelberg, Nora M; Kuusniemi, Kristiina; Neuvonen, Pertti J; Olkkola, Klaus T

    2011-06-01

    The aim of this study was to investigate the effect of the cytochrome P450 3A4 inhibitor clarithromycin on the pharmacokinetics and pharmacodynamics of oral oxycodone in young and elderly subjects. Ten young and 10 elderly healthy subjects participated in this placebo-controlled, randomized, 2-phase crossover study. Subjects took clarithromycin 500 mg or placebo twice daily for 5 days. On day 4, subjects ingested an oral dose of 10 mg oxycodone. Plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 hours, and pharmacological response for 12 hours. Clarithromycin decreased the apparent clearance of oxycodone by 53% in young and 48% in elderly subjects (P < 0.001) and prolonged its elimination half-life. The mean area under the plasma concentration-time curve (AUC0-∞) of oxycodone was increased by 2.0-fold (range, 1.3-fold to 2.7-fold) (P < 0.001) in young and 2.3-fold (range, 1.1-fold to 3.8-fold) (P < 0.001) in elderly subjects. The formation of noroxycodone was decreased by 74% in young and 71% in elderly subjects (P < 0.001). The ratio of AUC0-∞ of oxycodone during the clarithromycin phase compared with the one with placebo did not differ between the age groups. Clarithromycin did not alter the pharmacological response to oxycodone. Clarithromycin increased the exposure to oral oxycodone, but the magnitude of this effect was not age related. Although the pharmacological response to oxycodone was not significantly influenced by clarithromycin, dose reductions may be necessary in the most sensitive patients to avoid adverse effects when oxycodone is used concomitantly with clarithromycin.

  2. Calcium Control of Neurotransmitter Release

    PubMed Central

    Südhof, Thomas C.

    2012-01-01

    Upon entering a presynaptic terminal, an action potential opens Ca2+ channels, and transiently increases the local Ca2+ concentration at the presynaptic active zone. Ca2+ then triggers neurotransmitter release within a few hundred microseconds by activating synaptotagmins Ca2+. Synaptotagmins bind Ca2+ via two C2-domains, and transduce the Ca2+ signal into a nanomechanical activation of the membrane fusion machinery; this activation is mediated by the Ca2+-dependent interaction of the synaptotagmin C2-domains with phospholipids and SNARE proteins. In triggering exocytosis, synaptotagmins do not act alone, but require an obligatory cofactor called complexin, a small protein that binds to SNARE complexes and simultaneously activates and clamps the SNARE complexes, thereby positioning the SNARE complexes for subsequent synaptotagmin action. The conserved function of synaptotagmins and complexins operates generally in most, if not all, Ca2+-regulated forms of exocytosis throughout the body in addition to synaptic vesicle exocytosis, including in the degranulation of mast cells, acrosome exocytosis in sperm cells, hormone secretion from endocrine cells, and neuropeptide release. PMID:22068972

  3. Optimal dose of intravenous oxycodone for attenuating hemodynamic changes after endotracheal intubation in healthy patients

    PubMed Central

    Park, Yong-Hee; Lee, Seung-Hyuk; Lee, Oh Haeng; Kang, Hyun; Shin, Hwa-Yong; Baek, Chong-Wha; Jung, Yong Hun; Woo, Young Cheol

    2017-01-01

    Abstract Background: Intravenous oxycodone has been used as an adjunct to anesthetic agents. This study aimed to assess the optimal dose of intravenous oxycodone for the attenuation of the hemodynamic responses to laryngoscopy and endotracheal intubation. Methods: A prospective, randomized, double-blind study was conducted. Ninety-five patients were randomly divided into 5 groups based on the oxycodone dose: 0, 0.05, 0.1, 0.15, 0.2 mg/kg. After administering the assigned dose of intravenous oxycodone, anesthesia was induced with thiopental. Heart rate (HR) and blood pressure (BP) were measured at baseline, before intubation, and 1, 2, and 3 minutes after intubation. The percentage increase of BP was calculated as (highest BP after intubation − baseline BP)/baseline BP × 100 (%). The percentage increase of HR was calculated in same formula as above. Hypertension was defined as a 15% increase of systolic BP from baseline, and probit analysis was conducted. Results: Hemodynamic data from 86 patients were analyzed. The percentage increase of mean arterial pressure after intubation in groups 0.05, 0.1, 0.15, and 0.2 was significantly different from that in the control (P < 0.001). For HR, the percentage increase was lower than control group when oxycodone was same or more than 0.1 mg/kg (P < 0.05). Using probit analysis, the 95% effective dose (ED95) for preventing hypertension was 0.159 mg/kg (95% confidence interval [CI], 0.122–0.243). In addition, ED50 was 0.020 mg/kg (95% CI, −0.037 to 0.049). However, oxycodone was not effective for maintaining the HR in our study dosage. There were no significant differences in the incidence of hypotension during induction between groups. Conclusions: Using 0.1 mg/kg of intravenous oxycodone is sufficient to attenuate the increase of BP and HR during induction period in healthy patients. The ED95, which was 0.159 mg/kg, can be useful to adjust the dosage of IV oxycodone for maintain stable BP

  4. Opioid withdrawal presenting only nausea during tapering of oxycodone after celiac plexus block: a case report.

    PubMed

    Sakamoto, Akiyuki; Takayama, Hiroto; Mamiya, Keiko; Koizumi, Tomonobu

    2016-01-01

    Celiac plexus block (CPB) is an effective treatment for patients suffering pain. CPB may allow for a reduction in opioid dosage, and may alleviate some of the unwanted side effects of these drugs. However, there is a substantial risk of withdrawal symptoms after reduction of opioid dose. We describe a case of pancreatic cancer developing opioid withdrawal after CPB, who presented only nausea. A 70-year-old man was referred to our hospital due to severe pancreatic cancer pain. He was administered oxycodone (oxycontin®) at 240 mg per day, and presented nausea and anorexia as side effects. CPB was performed due to insufficient pain relief. His pain disappeared on the same day as treatment. Oxycodone was reduced to 160 mg/day, and further reduced two days later to 80 mg/day. However, he complained of more severe nausea and loss of appetite even after tapering of oxycodone. Physical examination, blood chemistry examination, and brain computed tomography (CT) showed no abnormalities. Administration of fast-release oxycodone (Oxinome®) at a dose of 10 mg immediately improved his nausea. There have been no previous reports of nausea as the sole symptom of opioid withdrawal. The present case indicates that unless opioid side effects improve after dosage reduction, the possibility that they may be withdrawal symptoms should also be considered.

  5. Comparison of relative oxycodone consumption in surgical pleth index-guided analgesia versus conventional analgesia during sevoflurane anesthesia

    PubMed Central

    Won, Young Ju; Lim, Byung Gun; Lee, So Hyun; Park, Sangwoo; Kim, Heezoo; Lee, Il Ok; Kong, Myoung Hoon

    2016-01-01

    Abstract Background: The surgical pleth index (SPI) is proposed for titration of analgesic drugs during general anesthesia. Several reports have investigated the effect of SPI on the consumption of opioids including remifentanil, fentanyl, and sufentanil during anesthesia, but there are no reports about oxycodone. We aimed to investigate intravenous oxycodone consumption between SPI-guided analgesia and conventional analgesia practices during sevoflurane anesthesia in patients undergoing thyroidectomy. Methods: Forty-five patients undergoing elective thyroidectomy were randomly assigned to an SPI group (SPI-guided analgesia group, n = 23) or a control group (conventional analgesia group, n = 22). Anesthesia was maintained with sevoflurane to achieve bispectral index values between 40 and 60. In the SPI group, oxycodone 1 mg was administered intravenously at SPI values over 50; in the control group, oxycodone 1 mg was administered intravenously at the occurrence of tachycardia or hypertension event. Intraoperative oxycodone consumption and extubation time were recorded. The number of hemodynamic and somatic movement events was recorded, as were postoperative pain and recovery scores. Results: Patients’ characteristics were comparable between the groups. Intraoperative oxycodone consumption in the SPI group was significantly lower than the control group (3.5 ± 2.4 vs 5.1 ± 2.4 mg; P = 0.012). Extubation time was significantly shorter in the SPI group (10.6 ± 3.5 vs 13.4 ± 4.6 min; P = 0.026). Hemodynamic and somatic movement events during anesthesia were comparable between the groups, as were numeric rating scales for pain and modified Aldrete scores at postanesthesia care unit. Conclusions: SPI-guided analgesia reduces intravenous oxycodone consumption and extubation time compared with conventional analgesia based on clinical parameters during sevoflurane anesthesia in patients undergoing thyroidectomy. PMID:27583920

  6. Controlling protein release using biodegradable microparticles

    NASA Astrophysics Data System (ADS)

    Kline, Benjamin Patrick

    Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety of development processes. This research aimed to identify microparticle formulations to control protein release and also to determine which formulation parameters affected burst release, encapsulation, and steady-state release the most. It was found that polymer type and composition were two of the most important factors. Long-term controlled release of bovine serum albumin (BSA) was achieved as well as a wide variety of release profiles. A method was identified for micronizing protein at low cost to retain activity and coacervation was evaluated as a method for preparing protein loaded microspheres. This research provides a basis from which researchers can create better controlled release formulations for future protein therapeutics.

  7. Controlled release polymeric ocular delivery of acyclovir.

    PubMed

    Deshpande, Praful Balavant; Dandagi, Panchaxari; Udupa, Nayanabhirama; Gopal, Shavi V; Jain, Samata S; Vasanth, Surenalli G

    2010-01-01

    The aim of the present study was to formulate and evaluate controlled release polymeric ocular delivery of acyclovir. Reservoir-type ocular inserts were fabricated by sandwiching hydroxypropyl methylcellulose (HPMC) matrix film containing acyclovir between two rate controlling membranes of cellulose acetate phthalate (CAP). The solubility and dissolution rate of poorly soluble acyclovir was enhanced by preparing binary systems with beta-cyclodextrin and then incorporated into HPMC matrix. Nine formulations (AB-1 to AB-9) with varying ratio of HPMC (drug matrix) and CAP (rate controlling membrane) were developed and sterilized by gamma radiation. The formulations were subjected to various physico-chemical evaluations. The in vitro release profile of all the formulations showed a steady, controlled drug release up to 20 h with non-Fickian diffusion behavior. A high correlation coefficient found between in vitro/in vivo release rate studies. Formation of acyclovir complex was confirmed by differential scanning calorimetry. In addition, dissolution rate studies revealed improved solubility of acyclovir when complexed with beta-cyclodextrin. Stability studies showed that the ocular inserts could be stored safely at study storage conditions. In conclusion, the present study demonstrated controlled release formulation of acyclovir inserts for ocular delivery using biodegradable polymers.

  8. An update on oxycodone: lessons for death investigators in Australia.

    PubMed

    Pilgrim, Jennifer L; Yafistham, Sabrina Putrianita; Gaya, Sanjeev; Saar, Eva; Drummer, Olaf H

    2015-03-01

    Oxycodone is one of the most abused prescription drugs. Iatrogenic factors that lead to oxycodone-related death, such as mis-prescribing, present an opportunity for death prevention if identified early. This study investigated deaths involving oxycodone in Australia to explore potentially inappropriate prescribing and the coroner's investigation. The National Coronial Information System identified cases from 2001 to 2011 where oxycodone was detected by toxicological analysis. There were 806 oxycodone-related deaths, with a significant increase in the 11-year period, from 21 deaths in 2001, up almost sevenfold in 2011 (139 deaths). Most deaths were caused by combined drug toxicity (63.4%) or oxycodone toxicity alone (11.8%). Most individuals were male (59.1%), aged 35-44 years (26.7%), who died unintentionally (56.4%), with mental illness (52.1%) and/or a history of acute or chronic pain (46.2%). 312 cases (39%) described a legitimate prescription for oxycodone, of which most involved non-cancer related chronic pain. About three quarters of the indications were deemed appropriate. There were at least 43 different indications treated with oxycodone that were inappropriate. The majority of oxycodone-related cases involved minor to no description of the drugs involved (n = 600; 74.4%). A moderate description of oxycodone involvement was given in 162 cases (20.1%), while only 44 cases (5.5%) involved a thorough examination and recommendations from the coroners on oxycodone and other drugs involved in death. This study emphasized the need for medical practitioners to exercise caution when prescribing oxycodone and for coroners to provide more consistent and detailed information regarding drug use, in order to identify and implement preventive strategies.

  9. Prenatal Oxycodone Exposure Impairs Spatial Learning and/or Memory in Rats

    PubMed Central

    Davis, Chris P.; Franklin, La’Tonya M.; Johnson, Gabriel S.; Schrott, Lisa M.

    2010-01-01

    Recent changes in demographic patterns of drug use have resulted in the increased non-medical use of prescription opiates. These users are younger and more likely to be female, which has the potential for increasing rates of in utero exposure. Therefore, we developed a rat model that simulates a prescription opiate-dependent woman who becomes pregnant. Adult female Sprague-Dawley rats were treated for 30 days via oral gavage with ascending doses of oxycodone HCl up to a final dose of 15 mg/kg/day, which was maintained during breeding and gestation. Controls were treated with water. The adult male offspring of these treated dams were tested on the radial arm maze, the Morris water maze (with a short and a long intertrial interval), and a spatial T-maze. Prenatal oxycodone exposure led to a deficit in the radial arm maze characterized by a greater number of reference memory errors, especially in the beginning of testing. In contrast, in the T-maze, prenatal oxycodone-exposed rats learned the task as well as well as the prenatal water controls. However, they had a modest deficit in retention of the task when assessed 5 days after acquisition training ended. For the Morris water maze, the intertrial interval affected the pattern of learning. While there was no deficit when the training had a short intertrial interval, when there was a long intertrial interval, prenatal oxycodone-exposed rats had poorer acquisition. The spatial learning deficit was characterized by and increased latency to find and a greater distance traveled to the platform in the prenatal oxycodone-exposed rats. These data were corroborated by analysis of the behavioral search strategy, which showed a decreased use of spatial strategies and an increase in non-spatial strategies, especially wall-hugging, in prenatal oxycodone-exposed rats as compared to prenatal water control rats on day 2 of acquisition. These results indicate that prenatal oxycodone exposure consistently impairs learning and memory

  10. Controlled drug release from bifunctionalized mesoporous silica

    SciTech Connect

    Xu Wujun; Gao Qiang; Xu Yao Wu Dong; Sun Yuhan; Shen Wanling; Deng Feng

    2008-10-15

    Serial of trimethylsilyl-carboxyl bifunctionalized SBA-15 (TMS/COOH/SBA-15) have been studied as carriers for controlled release of drug famotidine (Famo). To load Famo with large capacity, SBA-15 with high content of carboxyl groups was successfully synthesized by one-pot synthesis under the assistance of KCl. The mesostructure of carboxyl functionalized SBA-15 (COOH/SBA-15) could still be kept even though the content of carboxyl groups was up to 57.2%. Increasing carboxyl content could effectively enhance the loading capacity of Famo. Compared with pure SBA-15, into which Famo could be hardly adsorbed, the largest drug loading capacity of COOH/SBA-15 could achieve 396.9 mg/g. The release of Famo from mesoporous silica was studied in simulated intestine fluid (SIF, pH=7.4). For COOH/SBA-15, the release rate of Famo decreased with narrowing pore size. After grafting TMS groups on the surface of COOH/SBA-15 with hexamethyldisilazane, the release of Famo was greatly delayed with the increasing content of TMS groups. - Graphical abstract: Trimethylsilyl-carboxyl bifunctionalized SBA-15 has been studied as carrier for controlled release of drug famotidine. To load drug with large capacity, SBA-15 with high content of carboxyl groups was successfully synthesized. After grafting trimethylsilyl groups on the surface of carboxyl functionalized SBA-15, the release of Famo was greatly delayed with the increasing content of TMS groups.

  11. Controlled release reservoir mini tablets approach for controlling the drug release of Galantamine Hydrobromide.

    PubMed

    Khatavkar, Umesh Nandkumar; Shimpi, Shamkant Laxman; Kumar, K Jayaram; Deo, Kishor Dattatraya

    2012-01-01

    The objective of this study is to explore and investigate the reservoir mini tablets approach to control the release of Galantamine Hydrobromide in comparison to desired release profile to the Innovator formulation Razadyne ER capsules as disclosed in US Patent 7,160,559 which is granted to Janseen Pharmaceutica NV. The core mini tablets were prepared using the direct compression and wet granulation methods. These core mini tablets were further coated with Galantamine Hydrobromide in two different portions; 70% as controlled release and 30% as immediate release and then filled in empty hard gelatin capsule shells. The dissolution profiles of each formulation were compared to those of Razadyne ER capsules and the mean dissolution time (MDT), dissolution efficiency (DE%) and dissolution similarity (f2 factor) were calculated. It was observed that core formulation plays an important role in controlling the drug release as well as maintaining pH independent drug release profile. The release mechanism of GAH from reservoir mini tablet formulation follows Higuchi and first order. These results imply that controlled release reservoir mini tablets which further filled into empty hard gelatin capsule shells can be a suitable method to formulate controlled release Galantamine hydrobromide.

  12. Uniform biodegradable microparticle systems for controlled release

    PubMed Central

    Xia, Yujie; Pack, Daniel W.

    2014-01-01

    Drug delivery methods can impact efficacy as much as the nature of the drug itself. Microparticles made of biodegradable polymers such as poly(D,L-lactide-co-glycolide) and poly(lactic acid) (PLA) have been studied extensively for controlled release of diverse drugs. By using a modified solvent extraction/evaporation method called precision particle fabrication (PPF), uniform microparticles such as single-wall microspheres, double-wall microspheres and liquid-core microcapsules have been fabricated with precise control of their geometric structures. By producing particles of uniform size, which has crucial impact on drug release behaviors, PPF-fabricated microparticles provide unique insights about drug release mechanism. Using small-molecule and macromolecule model drugs, our group demonstrated that physicochemical properties of the polymers and drugs and structural properties of the matrix can greatly impact drug distribution within microparticles, particle erosion and drug release rates. By careful selection of particle size and shell thickness, uniform microparticles can achieve “zero-order”, pulsatile or tandem release of drugs. PMID:12106984

  13. Effects of ibudilast on oxycodone-induced analgesia and subjective effects in opioid-dependent volunteers.

    PubMed

    Cooper, Z D; Johnson, K W; Vosburg, S K; Sullivan, M A; Manubay, J; Martinez, D; Jones, J D; Saccone, P A; Comer, S D

    2017-09-01

    Opioid-induced glial activation is hypothesized to contribute to the development of tolerance to opioid-induced analgesia. This inpatient, double-blind, placebo-controlled, within-subject and between-groups pilot study investigated the dose-dependent effects of ibudilast, a glial cell modulator, on oxycodone-induced analgesia. Opioid-dependent volunteers were maintained on morphine (30mg, PO, QID) for two weeks and received placebo ibudilast (0mg, PO, BID) during the 1st week (days 1-7). On day 8, participants (N=10/group) were randomized to receive ibudilast (20 or 40mg, PO, BID) or placebo for the remainder of the study. On days 4 (week 1) and 11 (week 2), the analgesic, subjective, and physiological effects of oxycodone (0, 25, 50mg/70kg, PO) were determined. Analgesia was measured using the cold pressor test; participants immersed their hand in cold water (4°C) and pain threshold and pain tolerability were recorded. Oxycodone decreased pain threshold and tolerability in all groups during week 1. During week 2, the placebo group exhibited a blunted analgesic response to oxycodone for pain threshold and subjective pain ratings, whereas the 40mg BID ibudilast group exhibited greater analgesia as measured by subjective pain ratings (p≤0.05). Oxycodone also increased subjective drug effect ratings associated with abuse liability in all groups during week 1 (p≤0.05); ibudilast did not consistently affect these ratings. These findings suggest that ibudilast may enhance opioid-induced analgesia. Investigating higher ibudilast doses may establish the utility of pharmacological modulation of glial activity to maximize the clinical use of opioids. Copyright © 2017. Published by Elsevier B.V.

  14. Preventing and controlling accidental gas releases

    NASA Astrophysics Data System (ADS)

    Moskowitz, P. D.; Fthenakis, V. M.; Kalb, P. D.

    1988-07-01

    Toxic, flammable, and explosive gases may be used in photovoltaic cell research laboratories and in commercial manufacturing facilities. Accidental release of these materials can present hazards to life and property. Accidents can arise from a variety of mechanical and human related failures. These can occur from the time materials are received at the loading dock of the facility to the time treated gases are discharged to the atmosphere through a stack. Each type of initiating event may require a different control approach. These may range from the training and certification of plant workers charged with the handling of gas cylinder hookups to installation of emergency pollution control systems. Since engineering options for controlling released materials are limited, emphasis should be placed on administrative and engineering approaches for preventing such accidents. These are likely to be the most effective approaches for protecting life and property.

  15. EPICS application source/release control

    SciTech Connect

    Zieman, B.; Anderson, J.; Kraimer, M

    1995-12-31

    This manual describes a set of Application Source/Release Control tools (appSR) that can be used to develop software for EPICS based control systems. The Application Source/Release Control System (appSR) has been unbundled from base EPICS and is now available as an EPICS extension. Due to this unbundling, two new directories must be added to a user`s path (see section ``Environment`` on page 3 for more information) and a new command getapp must be issued after the getrel command to get a specific version of appSR (see section ``Creating The Initial Application System Area`` on page 7 for more information). It is now required that GNU make version 3.71 or later be used for makes instead of SUN make. Users should now type gmake instead of make.

  16. Tapentadol extended release for chronic pain patients.

    PubMed

    Taylor, Robert; Pergolizzi, Joseph V; Raffa, Robert B

    2013-01-01

    Chronic pain reduces quality of life, utilizes healthcare resources, and increases healthcare costs. It is widespread, but generally inadequately treated or managed, partly due to several obstacles, including a limited number of mechanistic options for long-term pharmacologic agents. Opioids are generally the primary class of analgesic prescribed, but because of associated side effects during long-term treatment, many patients become noncompliant or discontinue treatment. A long-term use analgesic with a good benefit/risk ratio is advantageous. A literature search for randomized trials using tapentadol extended release (ER) for noncancer chronic pain patients was conducted. Databases searched included PubMed, MEDLINE, EMBASE, and Google Scholar, using key terms "tapentadol," "prolonged release," "extended release," and "chronic pain" individually or in combination. The results were synthesized and evaluated. A total of six randomized, controlled studies were identified. Chronic pain conditions analyzed included low back, osteoarthritis, and diabetic peripheral neuropathy. Treatment arms consisted most often of placebo, tapentadol ER (100-250 mg twice daily [b.i.d.]), and/or oxycodone CR (controlled release) (20-50 mg b.i.d.). Subjects treated with tapentadol ER had significant reduction in pain intensity compared to placebo controls and similar efficacy to oxycodone CR. Overall, the safety profile was superior to that of oxycodone CR in regards to reduction in side effects, reduced severity of side effects (particularly gastrointestinal related), and lower study discontinuation rates. The two mechanisms of analgesic action of tapentadol, combined with an ER, appears to provide equal efficacy to a strong controlled-release opioid while providing greater gastrointestinal tolerability. The reduction in incidence and severity of gastrointestinal side effects correlated with a higher compliance rate. These findings suggest that tapentadol ER might be a viable

  17. Analgesic studies of codeine and oxycodone in patients with cancer. II. Comparisons of intramuscular oxycodone with intramuscular morphine and codeine.

    PubMed

    Beaver, W T; Wallenstein, S L; Rogers, A; Houde, R W

    1978-10-01

    The relative analgesic potency of single graded intramuscular doses of oxycodone and morphine was evaluated in a double-blind study in patients with chronic pain due to cancer. When both intensity and duration of analgesia are considered (total analgesic effect), oxycodone was 2/3 to 3/4 as potent as morphine, while in terms of peak analgesia, it was 8/10 to equipotent. In doses producing equivalent peak effect, oxycodone had a shorter duration of action than morphine. Intramuscular oxycodone was also compared to intramuscular codeine in a similar patient group. In terms of total analgesic effect, oxycodone was 10 times as potent as codeine, while in terms of peak analgesia it was 12 times as potent. These relative potency relationships of oxycodone, taken in conjunction with the oral/parenteral potency ratios of codeine and oxycodone established in the previous paper and several previous relative potency assays involving morphine, oxymorphone and codeine, demonstrate a highly consistent pattern of analgesic structure-activity relationships encompassing morphine, oxymorphone, codeine and oxycodone. The results of these studies do not appear to support the hypothesis that, in man, the analgesic activity of codeine is due to its O-demethylation to morphine.

  18. Decreased responsiveness to oxycodone: A case of a pharmacokinetic drug interaction?

    PubMed

    Pon, Doreen; Hwang, Joon; Lo, Teresa; Zyl, Carin Van

    2015-01-01

    Concurrent administration of oxycodone and phenytoin may cause, through induction of CYP3A4 enzymes, decreased analgesic effects of oxycodone. However, no descriptions of this interaction exist. A patient who was on oxycodone for chronic back pain was admitted to the hospital. Five days after initiating fosphenytoin, the patient experienced a dramatic escalation in his pain and lack of response to oxycodone breakthrough doses. Changing oxycodone to hydromorphone resulted in significantly improved analgesia. Concurrent use of fosphenytoin and oxycodone may increase the conversion of oxycodone to inactive metabolites, resulting in decreased analgesia. This may be avoided using hydromorphone, morphine, or oxymorphone.

  19. Meltable magnetic biocomposites for controlled release

    NASA Astrophysics Data System (ADS)

    Müller, R.; Zhou, M.; Dellith, A.; Liebert, T.; Heinze, T.

    2017-06-01

    New biocompatible composites with adjustable melting point in the range of 30-140 °C, consisting of magnetite nanoparticles embedded into a matrix of meltable dextran fatty acid ester are presented which can be softened under an induced alternating magnetic field (AMF). The chosen thermoplastic magnetic composites have a melting range close to human body temperature and can be easily shaped into disk or coating film under melting. The composite disks were loaded with green fluorescent protein (GFP) as a model protein. Controlled release of the protein was realized with high frequent alternating magnetic field of 20 kA/m at 400 kHz. These results showed that under an AMF the release of GFP from magnetic composite was accelerated compared to the control sample without exposure to AMF. Furthermore a texturing of particles in the polymer matrix by a static magnetic field was investigated.

  20. Controlled release fertilizer workshop, 1991: Proceedings

    SciTech Connect

    Scheib, R.M.

    1991-11-01

    Over the last 20 years the Tennessee Valley Authority`s National Fertilizer and Environmental Research Center (NFERC) has carried out a number of programs to develop controlled release fertilizers. They pioneered the development and commercialization of sulfur coated urea and conducted extensive research in an attempt to develop an economical synthesis for oxamide. In recent years there has developed an increasing interest in the environmental impact of fertilizers, particularly on the potential for ground water contamination by nitrate derived from fertilizer materials. In response to this interest NFERC`s Chemical Research Department organized a five member Controlled Release Fertilizer (CRF) Team to reassess the potential for controlled release materials in agriculture with a view to minimizing any adverse environmental impact and increasing the efficiency of nutrient utilization by the crop. This workshop was part of that reassessment program. The workshop goals were: To determine the present status of CRF research, production and use; to assess the future needs of CRF producers and consumers; and to promote communication and exchange of information. To accomplish these goals the team invited speakers from across` the United States representing academics, experimental station researchers, fertilizer producers, environmentalists, and marketing experts to present papers.

  1. Controlled release fertilizer workshop, 1991: Proceedings

    SciTech Connect

    Scheib, R.M.

    1991-11-01

    Over the last 20 years the Tennessee Valley Authority's National Fertilizer and Environmental Research Center (NFERC) has carried out a number of programs to develop controlled release fertilizers. They pioneered the development and commercialization of sulfur coated urea and conducted extensive research in an attempt to develop an economical synthesis for oxamide. In recent years there has developed an increasing interest in the environmental impact of fertilizers, particularly on the potential for ground water contamination by nitrate derived from fertilizer materials. In response to this interest NFERC's Chemical Research Department organized a five member Controlled Release Fertilizer (CRF) Team to reassess the potential for controlled release materials in agriculture with a view to minimizing any adverse environmental impact and increasing the efficiency of nutrient utilization by the crop. This workshop was part of that reassessment program. The workshop goals were: To determine the present status of CRF research, production and use; to assess the future needs of CRF producers and consumers; and to promote communication and exchange of information. To accomplish these goals the team invited speakers from across' the United States representing academics, experimental station researchers, fertilizer producers, environmentalists, and marketing experts to present papers.

  2. Retrospective Evaluation of a Fixed-Dose Combination of Oxycodone and Acetaminophen to Manage Moderate Pain: The Lower the Better.

    PubMed

    Natoli, Silvia; Lazzari, Marzia; Carpenedo, Roberta; Palombo, Elisa; Silvi, Maria Beatrice; Mammucari, Massimo; Dauri, Mario

    2016-06-01

    Oxycodone is one of the most commonly used opioid analgesics in the clinical management of pain. The present retrospective analysis aimed to determine the dose of oxycodone that could achieve effective control of moderate pain when combined with a fixed dose of acetaminophen, and the time required to reach a clinically relevant reduction in intensity of pain. Data of patients treated with a combination of oxycodone (5, 10, and 20 mg) and acetaminophen (325 mg) were evaluated for gender, current disease condition, basal pain intensity, total daily dose, days of controlled pain at the initial low dose, and pain intensity after treatment using a numeric pain rating scale. Data from a total of 491 patients were assessed; of these 93.5% of patients experienced persistent non-cancer pain and had an average baseline pain score of 5.68 ± 1.35. For the overall population, the pain score was reduced to 2.49 ± 1.71 with a mean dose of 8.68 ± 4.96 mg oxycodone after 21.60 ± 6.12 days of treatment with the combination. Almost 97% of the patients who reported relief of pain received 1.61 ± 0.67 doses of oxycodone 5 mg combined with 325 mg of acetaminophen. A low-dose combination of oxycodone with acetaminophen can be effective in the management of moderate pain and may help in reducing the treatment-associated adverse reactions and drug dependence. Sponsorship for article processing charges was provided by Molteni Farmaceutici, Florence, Italy.

  3. Oxycodone/paracetamol: a low-dose synergic combination useful in different types of pain.

    PubMed

    Gatti, Antonio; Sabato, Elisabetta; Di Paolo, Anna Rita; Mammucari, Massimo; Sabato, Alessandro Fabrizio

    2010-01-01

    The combination of two analgesic agents offers several advantages in the treatment of chronic pain. Paracetamol (acetaminophen) has central analgesic activity without a nonsteroidal anti-inflammatory drug (NSAID)-like or opioid-like effect. Oxycodone is a semisynthetic opioid agonist. The oral fixed-dose combination of oxycodone and paracetamol immediate-release formulation has a synergistic mechanism of action that is useful for moderate-to-severe pain and for nonresponders to NSAIDs or paracetamol alone. This fixed-dose combination offers several advantages: lower individual drug doses can be used because of their synergistic mechanisms of action, its opioid-sparing effect and it has a good efficacy and tolerability profile. Efficacy and safety of this fixed-dose combination were assessed in a wide range of clinical settings: in patients with osteoarthritis or chronic musculoskeletal pain, including when complicated by a neuropathic component; for chronic pain in elderly patients; cancer-related pain; postoperative pain; and for neuropathic pain, in the latter case usually given in combination with an NSAID or other drugs. The large variety of indications for which this fixed-dose combination may be useful can be attributed to the pharmacological synergy between oxycodone and paracetamol and because lower individual drug dosages can be used, suggesting that this should be a first-line agent for the treatment of chronic moderate-to-severe pain.

  4. Injectable controlled release depots for large molecules

    PubMed Central

    Schwendeman, Steven P.; Shah, Ronak B.; Bailey, Brittany A.; Schwendeman, Anna S.

    2014-01-01

    Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few “real world” biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LAR products, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development. PMID:24929039

  5. Injectable controlled release depots for large molecules.

    PubMed

    Schwendeman, Steven P; Shah, Ronak B; Bailey, Brittany A; Schwendeman, Anna S

    2014-09-28

    Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few "real world" biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LARproducts, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development.

  6. Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

    PubMed

    Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

    2013-09-01

    This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

  7. Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts

    PubMed Central

    Comer, Sandra D; Metz, Verena E; Cooper, Ziva D; Kowalczyk, William J; Jones, Jermaine D; Sullivan, Maria A; Manubay, Jeanne M; Vosburg, Suzanne K; Smith, Mary E; Peyser, Deena; Saccone, Phillip A

    2014-01-01

    This double-blind, placebo-controlled study investigated effects of oral morphine (0, 45, 135 mg/70kg) and oral oxycodone (0, 15, 45 mg/70kg) in buprenorphine-maintained opioid addicts. Since a 3:1 morphine:oxycodone dose ratio had yielded equivalent subjective and physiological effects in non-dependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures, i.e. a drug vs. money and a drug vs. drug procedure, were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater compared to high-dose morphine. The study demonstrated that a 3:1 dose ratio of morphine:oxycodone was not equipotent in buprenorphine-dependent subjects. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest. PMID:23839029

  8. Within-subject comparison of the psychopharmacological profiles of oral oxycodone and oral morphine in non-drug-abusing volunteers

    PubMed Central

    Lichtor, Stephanie A.

    2008-01-01

    Rationale Nonmedical use and abuse of prescription opioids is a significant problem in the USA. Little attention has been paid to assessing the relative psychopharmacological profile (including abuse liability-related effects) of specific prescription opioids. Objectives The aim of this study is to directly compare the psychopharmacological profile of two oral opioids within the same subject. Methods A randomized, placebo-controlled, crossover study was done in which 20 non-drug-abusing volunteers ingested 10 and 20 mg of oxycodone, 30 and 60 mg of morphine, and placebo in separate sessions. Drug doses were equated on an objective measure of opiate effects: miosis. Subjective, psychomotor, reinforcing, and physiological effects of the opioids were assessed. Results In general, the two opioids at equimiotic doses produced similar prototypic opiate-like effects and psychomotor impairment of similar magnitude. However, several effects were found only with 20 mg oxycodone. Both drugs produced abuse liability-related subjective effects but also dysphoric effects, particularly with 60 mg morphine. Neither drug at either dose functioned as a reinforcer, as measured by the Multiple Choice Procedure. Relative potency ratios indicated an average oxycodone:morphine ratio of 1:3. Conclusions The psychopharmacological profile of oxycodone and morphine at equimiotic doses had many similarities; however, differences were found in producing abuse liability-related and dysphoric effects. In the medical community, it is commonly accepted that oral oxycodone is 1.5 to 2 times as potent as oral morphine in producing analgesia; using this ratio, although patients may experience similar degrees of pain relief, those receiving oxycodone may be experiencing stronger and potentially different psychopharmacological effects. PMID:17899018

  9. Controlled Release Formulations of Auxinic Herbicides

    NASA Astrophysics Data System (ADS)

    Kowalski, Witold J.; Siłowiecki, Andrzej.; Romanowska, Iwona; Glazek, Mariola; Bajor, Justyna; Cieciwa, Katarzyna; Rychter, Piotr

    2013-04-01

    Controlled release formulations are applied extensively for the release of active ingredients such as plant protection agents and fertilizers in response to growing concern for ecological problems associated with increased use of plant protection chemicals required for intensive agricultural practices [1]. We synthesized oligomeric mixtures of (R,S)-3-hydroxy butyric acid chemically bonded with 2,4-D, Dicamba and MCPA herbicides (HBA) respectively, and determined their molecular structure and molecular weight dispersion by the size exclusion chromatography, proton magnetic resonance spectrometry and electro-spray ionization mass spectrometry. Further we carried out bioassays of herbicidal effectiveness of the HBA herbicides vs. series of dicotyledonous weeds and crop injury tests [2, 3, 4]. Field bioassays were accomplished according to the EPPO standards [5]. Groups of representative weeds (the development stages in the BCCH scale: 10 - 30) were selected as targets. Statistical variabilities were assessed by the Fisher LSD test for plants treated with the studied herbicides in form of HBA oligomers, the reference herbicides in form of dimethyl ammonium salts (DMA), and untreated plants. No statistically significant differences in the crop injuries caused by the HBA vs. the DMA reference formulation were observed. The effectiveness of the HBA herbicides was lower through the initial period (ca. 2 weeks) relative to the DMA salts, but a significant increase in the effectiveness of the HBA systems followed during the remaining fraction of each assay. After 6 weeks all observed efficiencies approached 100%. The death of weeds treated with the HBA herbicides was delayed when compared with the DMA reference herbicides. The delayed uptake observed for the HBA oligomers relative to the DMA salts was due to controlled release phenomena. In case of the DMA salts the total amount of active ingredients was available at the target site. By contrast, the amount of an active

  10. Control of bisphosphonate release using hydroxyapatite granules.

    PubMed

    Seshima, Hisashi; Yoshinari, Masao; Takemoto, Shinji; Hattori, Masayuki; Kawada, Eiji; Inoue, Takashi; Oda, Yutaka

    2006-08-01

    The efficacy of hydroxyapatite (HAp) as a carrier was investigated to establish a method of local administration of bisphosphonates (Bps), which has currently been administered systemically. HAp granules (300-500 microm in size) with different physicochemical features were prepared by altering the sintering temperature. To ascertain the physicochemical properties of the HAp granules, their crystallinity was assessed using X-ray diffraction, the surface morphology was examined under scanning electron microscopy, and the specific surface area and calcium dissolution were evaluated. Different Bps-HAp composites were subsequently prepared and the concentration of Bps released from these composites was measured. The influence of Bps-HAp composites on the rate of osteoclast survival was also evaluated. The results revealed that (1) HAp solubility depends on the sintering temperature; (2) The concentration of released Bps could be controlled by regulating the sintering temperature of HAp as a carrier; and (3) Bps released from Bps-HAp composites reduced the number of osteoclasts. These findings indicated that Bps-HAp composites could be locally administered as a drug delivery system to areas with bone resorption.

  11. Temperature-Controlled Clamping and Releasing Mechanism

    NASA Technical Reports Server (NTRS)

    Rosing, David; Ford, Virginia

    2005-01-01

    A report describes the development of a mechanism that automatically clamps upon warming and releases upon cooling between temperature limits of approx. =180 K and approx. =293 K. The mechanism satisfied a need specific to a program that involved repeated excursions of a spectrometer between a room-temperature atmospheric environment and a cryogenic vacuum testing environment. The mechanism was also to be utilized in the intended application of the spectrometer, in which the spectrometer would be clamped for protection during launch of a spacecraft and released in the cold of outer space to allow it to assume its nominal configuration for scientific observations. The mechanism is passive in the sense that its operation does not depend on a control system and does not require any power other than that incidental to heating and cooling. The clamping and releasing action is effected by bolt-preloaded stacks of shape-memory-alloy (SMA) cylinders. In designing this mechanism, as in designing other, similar SMA mechanisms, it was necessary to account for the complex interplay among thermal expansion, elastic and inelastic deformation under load, and SMA thermomechanical properties.

  12. A rapid technique for prediction of nutrient release from controlled release fertilizers

    USDA-ARS?s Scientific Manuscript database

    Nutrient release from soluble granular fertilizers can be modified by polymer coating to extend the total duration nutrient release up to 3 to 9 months and rate of release to match the nutrient requirement of the plant during the growing period. Hence these products are termed as “Controlled Release...

  13. 28 CFR 541.50 - Release from a control unit.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Release from a control unit. 541.50... INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control unit. (a) Only the Executive Panel may release an inmate from a control unit. The following factors...

  14. A Responsive Battery with Controlled Energy Release.

    PubMed

    Wang, Xiaopeng; Gao, Jian; Cheng, Zhihua; Chen, Nan; Qu, Liangti

    2016-11-14

    A new type of responsive battery with the fascinating feature of pressure perceptibility has been developed, which can spontaneously, timely and reliably control the power outputs (e.g., current and voltage) in response to pressure changes. The device design is based on the structure of the Zn-air battery, in which graphene-coated sponge serves as pressure-sensitive air cathode that endows the whole system with the capability of self-controlled energy release. The responsive batteries exhibit superior battery performance with high open-circuit voltage (1.3 V), and competitive areal capacity of 1.25 mAh cm(-2) . This work presents an important move towards next-generation intelligent energy storage devices with energy management function.

  15. RAPID DOPAMINE TRANSMISSION WITHIN THE NUCLEUS ACCUMBENS DRAMATICALLY DIFFERS FOLLOWING MORPHINE AND OXYCODONE DELIVERY

    PubMed Central

    Mabrouk, Omar S.; Lovic, Vedran; Singer, Bryan F.; Kennedy, Robert T.; Aragona, Brandon J.

    2014-01-01

    While most drugs of abuse increase dopamine neurotransmission, rapid neurochemical measurements show that different drugs evoke distinct dopamine release patterns within the nucleus accumbens. Rapid changes in dopamine concentration following psychostimulant administration have been well studied; however, such changes have never been examined following opioid delivery. Here, we provide novel measures of rapid dopamine release following intravenous infusion of two opioids, morphine and oxycodone, in drug naïve rats using fast-scan cyclic voltammetry and rapid (1 min) microdialysis coupled with mass spectrometry. In addition to measuring rapid dopamine transmission, microdialysis HPLC-MS measures changes in GABA, glutamate, monoamines, monoamine metabolites, and several other neurotransmitters. Although both opioids increased dopamine release in the nucleus accumbens, their patterns of drug-evoked dopamine transmission differed dramatically. Oxycodone evoked a robust and stable increase in dopamine concentration and a robust increase in the frequency and amplitude of phasic dopamine release events. Conversely, morphine evoked a brief (~ 1 min) increase in dopamine that was coincident with a surge in GABA concentration and then both transmitters returned to baseline levels. Thus, by providing rapid measures of neurotransmission, this study reveals previously unknown differences in opioid-induced neurotransmitter signaling. Investigating these differences may be essential for understanding how these two drugs of abuse could differentially usurp motivational circuitry and powerfully influence behavior. PMID:25208732

  16. Evaluation of ongoing oxycodone abuse among methadone-maintained patients.

    PubMed

    Dunn, Kelly E; Sigmon, Stacey C; McGee, Mark R; Heil, Sarah H; Higgins, Stephen T

    2008-12-01

    Prevalence of prescription opioid abuse has increased dramatically in recent years in the United States generally, and a similar pattern of increasing prescription opioid use has also been noted among patients seeking treatment for opioid dependence. This study presents results from an internal quality assurance project conducted by an outpatient methadone maintenance (MM) treatment clinic which sought to examine the extent of ongoing oxycodone abuse among patients that might be going undetected with current urinalysis-testing methods. One hundred five MM patients provided 437 urine samples over a 6-week period. Samples were analyzed using the clinic's usual enzyme multiplied immunoassay test (EMIT) opiate assay (300 ng/ml opiate cutpoint) and a supplemental oxycodone test strip (100 ng/ml oxycodone cutpoint). The EMIT assay identified only 6% (20/437) of samples as positive for oxycodone, whereas the oxycodone test strip indicated that 19% (83/437) tested positive for recent oxycodone use. Inspection of patient characteristics revealed that oxycodone users were more likely to report a prescription opioid as their primary drug at intake, be in MM treatment for a significantly shorter duration, and provide significantly more opioid- and cocaine-positive urine samples. Overall, these data illustrate the potential importance of monitoring for ongoing oxycodone use in MM clinics. Although future efforts should examine this question using more rigorous experimental methods, findings from this initial project have implications for clinical issues such as evaluating patient stability in treatment, making medication-dosing decisions, and determining patient eligibility for methadone take-home privileges.

  17. Pharmacokinetics and pharmacodynamics of once-daily controlled-release oxybutynin and immediate-release oxybutynin.

    PubMed

    Reiz, Joseph L; Salem, Paulette; Darke, Andrew C

    2007-03-01

    Oxybutynin is used to treat patients with urinary urgency, frequency, and urge incontinence. In this 2-way, multiple-dose, crossover study, the pharmacokinetics and pharmacodynamics of once-daily controlled-release oxybutynin were compared with immediate-release oxybutynin. Eighteen healthy male volunteers received one 15-mg controlled-release oxybutynin tablet once daily for 5 days or one 5-mg immediate-release oxybutynin tablet every 8 hours for 5 days. The washout period between treatments was > or =7 days. The mean steady-state AUC for oxybutynin following controlled-release oxybutynin treatment was higher (73.0 ng.h/mL) than following immediate-release oxybutynin treatment (53.6 ng.h/mL) (P = .0001). The mean C(max) was lower for controlled-release oxybutynin (5.7 ng/mL) than for immediate-release oxybutynin (7.5 ng/mL) (P = .0051), with a smaller fluctuation in oxybutynin plasma concentration for controlled-release oxybutynin (135.6%) than for immediate-release oxybutynin (319.3%) (P = .0001). Mean stimulated saliva output was greater for controlled-release oxybutynin, and mean dry mouth severity was less than immediate-release oxybutynin.

  18. Controlled release of water-soluble herbicides

    SciTech Connect

    Riggle, B.D.

    1985-01-01

    Pine kraft lignin was used to control the release of metribuzin (4-amino-6-tert-butyl-3-(methylthio)-as-triazin-5(4H)-one) and alachlor (2-chloro-2',6'-diethyl-N-methoxy-methyl acetanalide). Soil thin layer chromatography (TLC) analysis using /sup 14/C-metribuzin and /sup 14/C-alachlor demonstrated that NB-5203-58 series and PC940 series kraft lignins could retard the mobility of both herbicides after multiple soil TLC plate developments with water. Soil column chromatography analysis demonstrated that PC940C could retard the mobility of both herbicides after soil column water leaching by positioning the herbicides in the top portion of the soil column where the PC940C-herbicide mixture had been applied. There was a concentration effect where, as more PC940C was used, more /sup 14/C-labelled herbicide was retained in the top portion of the soil columns. Soil column chromatography and soil TLC plate analysis demonstrated that /sup 3/H-PC940C was immobile. Finally, PC940C significantly reduced metribuzin related phytotoxicity to field and greenhouse grown soybeans (Glycine max (L.) Merr.) which had been treated with PC940C rates of 0.77 and 1.15 L/ha and metribuzin rates of 0.42 and 0.84 kg/ha. The results for /sup 14/C-metribuzin and /sup 14/C-alachlor as well as the reduction in metribuzin related phytotoxicity to soybeans suggests that PC940C can effectively control the release of metribuzin and alachlor.

  19. Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety

    PubMed Central

    Samer, CF; Daali, Y; Wagner, M; Hopfgartner, G; Eap, CB; Rebsamen, MC; Rossier, MF; Hochstrasser, D; Dayer, P; Desmeules, JA

    2010-01-01

    Background and purpose: The major drug-metabolizing enzymes for the oxidation of oxycodone are CYP2D6 and CYP3A. A high interindividual variability in the activity of these enzymes because of genetic polymorphisms and/or drug–drug interactions is well established. The possible role of an active metabolite in the pharmacodynamics of oxycodone has been questioned and the importance of CYP3A-mediated effects on the pharmacokinetics and pharmacodynamics of oxycodone has been poorly explored. Experimental approach: We conducted a randomized crossover (five arms) double-blind placebo-controlled study in 10 healthy volunteers genotyped for CYP2D6. Oral oxycodone (0.2 mg·kg−1) was given alone or after inhibition of CYP2D6 (with quinidine) and/or of CYP3A (with ketoconazole). Experimental pain (cold pressor test, electrical stimulation, thermode), pupil size, psychomotor effects and toxicity were assessed. Key results: CYP2D6 activity was correlated with oxycodone experimental pain assessment. CYP2D6 ultra-rapid metabolizers experienced increased pharmacodynamic effects, whereas cold pressor test and pupil size were unchanged in CYP2D6 poor metabolizers, relative to extensive metabolizers. CYP2D6 blockade reduced subjective pain threshold (SPT) for oxycodone by 30% and the response was similar to placebo. CYP3A4 blockade had a major effect on all pharmacodynamic assessments and SPT increased by 15%. Oxymorphone Cmax was correlated with SPT assessment (ρS= 0.7) and the only independent positive predictor of SPT. Side-effects were observed after CYP3A4 blockade and/or in CYP2D6 ultra-rapid metabolizers. Conclusions and implications: The modulation of CYP2D6 and CYP3A activities had clear effects on oxycodone pharmacodynamics and these effects were dependent on CYP2D6 genetic polymorphism. PMID:20590588

  20. G protein-gated inwardly rectifying potassium (KIR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites

    PubMed Central

    Nakamura, Atsushi; Fujita, Masahide; Ono, Hiroko; Hongo, Yoshie; Kanbara, Tomoe; Ogawa, Koichi; Morioka, Yasuhide; Nishiyori, Atsushi; Shibasaki, Masahiro; Mori, Tomohisa; Suzuki, Tsutomu; Sakaguchi, Gaku; Kato, Akira; Hasegawa, Minoru

    2014-01-01

    BACKGROUND AND PURPOSE Oxycodone and morphine are μ-opioid receptor agonists prescribed to control moderate-to-severe pain. Previous studies suggested that these opioids exhibit different analgesic profiles. We hypothesized that distinct mechanisms mediate the differential effects of these two opioids and investigated the role of G protein-gated inwardly rectifying potassium (KIR3 also known as GIRK) channels in their antinociceptive effects. EXPERIMENTAL APPROACH Opioid-induced antinociceptive effects were assessed in mice, using the tail-flick test, by i.c.v. and intrathecal (i.t.) administration of morphine and oxycodone, alone and following inhibition of KIR3.1 channels with tertiapin-Q (30 pmol per mouse, i.c.v. and i.t.) and KIR3.1-specific siRNA. The antinociceptive effects of oxycodone and morphine were also examined after tertiapin-Q administration in the mouse femur bone cancer and neuropathic pain models. KEY RESULTS The antinociceptive effects of oxycodone, after both i.c.v. and i.t. administrations, were markedly attenuated by KIR3.1 channel inhibition. In contrast, the antinociceptive effects of i.c.v. morphine were unaffected, whereas those induced by i.t. morphine were attenuated, by KIR3.1 channel inhibition. In the two chronic pain models, the antinociceptive effects of s.c. oxycodone, but not morphine, were inhibited by supraspinal administration of tertiapin-Q. CONCLUSION AND IMPLICATIONS These results demonstrate that KIR3.1 channels play a primary role in the antinociceptive effects of oxycodone, but not those of morphine, at supraspinal sites and suggest that supraspinal KIR3.1 channels are responsible for the unique analgesic profile of oxycodone. PMID:24117458

  1. A Rapid Test for Prediction of Nutrient Release from Controlled Release Fertilizers

    USDA-ARS?s Scientific Manuscript database

    Nutrient release from soluble granular fertilizers can be modified by polymer coating. The coating technology can be fine-tuned to change the duration (3 to 9 months) and rate of nutrient release, hence these products are termed as controlled release fertilizers (CRF). There is a need to develop a r...

  2. 28 CFR 541.50 - Release from a control unit.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... general population of the institution which has a control unit. ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Release from a control unit. 541.50... INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control...

  3. Factors controlling gastric-glucagon release.

    PubMed Central

    Lefèbvre, P J; Luyckx, A S

    1977-01-01

    A system consisting of an isolated dog stomach perfused with whole blood has been designed to study gastric glucagon secretion. Under basal conditions, gastric glucagon release was 0.0-3.1 ng glucagon/100g of stomach per min. Arginine, at an arterial plasma concentration averaging 10 mM, elicited a rapid glucagon release. This gastric glucagon release was almost completely abolished by somatostatin (100 ng/ml). The release of gastric glucagon was not affected by hyperglycemia alone but was reduced by about 40% when hyperglycemia was concomitant with an hyperinsulinemia within the physiological range. These observations support the concept that adequate concentrations of insulin are necessary in order for hyperglycemia to inhibit gastric glucagon secretion. Furthermore, it is suggested that the isolated perfused dog stomach might provide a unique tool permitting investigation of alpha-cell function in the absence of endogenously released insulin. PMID:845258

  4. The analgesic efficacy of oxycodone hydrochloride versus fentanyl during outpatient artificial abortion operation: A randomized trial.

    PubMed

    Xie, Kangjie; Zhang, Wen; Fang, Wumei; Lian, Yanhong; Lin, Sufeng; Fang, Jun

    2017-06-01

    Problems like body movement, respiratory depression, and complained of pain are still common phenomenon in outpatient artificial abortion general anesthesia. Oxycodone hydrochloride is a semisynthetic opioid and has a good therapeutic effect on visceral pain. We hypothesize that oxycodone hydrochloride would be superior to fentanyl in outpatient artificial abortion surgery. In this clinical trial 149 American Society of Anesthesiologists (ASA) I or II female outpatients scheduled for elective artificial abortion surgeries under general anesthesia were randomly divided into 3 groups: oxycodone hydrochloride 0.06 mg/kg group (group A), oxycodone hydrochloride 0.08 mg/kg group (group B), and control group fentanyl 2 ug/kg (group C). The primary outcome was level body movement and respiratory depression during the surgery, the second outcome included the visual analogue scale (VAS) score 30 minutes after waking. A total of 120 participants completed the study, n = 40 in each group. There was no significant difference in patients' age, body mass index (BMI), preoperative heart rate, mean arterial blood pressure, consumption dose of propofol, intraoperative body movement type and times, and duration of surgery among the 3 groups (P > .05). Comparing the incidence of intraoperative respiratory depression and SPO2 < 90% among the 3 groups, group C's was significantly higher than those of groups A and B, and the difference was statistically significant (P < .05). Group A had no difference compared with group B. In VAS score 30minutes after waking, group C was the highest, followed by group A, with group B as the lowest. The difference among the 3 groups was statistically significant (P < .05), but a difference delta less than 1 on the VAS scale is not clinically significant. The analgesic effect of oxycodone hydrochloride at 0.06 mg/kg applied to painless artificial abortion surgery is not superior than that of fentanyl, but the incidence of

  5. Application of curdlan to controlled drug delivery. III. Drug release from sustained release suppositories in vitro.

    PubMed

    Kanke, M; Tanabe, E; Katayama, H; Koda, Y; Yoshitomi, H

    1995-08-01

    The use of curdlan, a natural beta-1,3-glucan, in the preparation of sustained release suppositories was studied in vitro. To prepare the suppositories, indomethacin, prednisolone or salbutamol sulfate was mixed with curdlan gel. Preparation conditions, including heating time and curdlan concentrations of 5 and 10%, had little effect on the drug release. The tonicity (hypotonic or isotonic) of the media for the suppository preparation and for in vitro drug release study also had little effect on drug release. However, the heating temperature during gel preparation, the drug amount in the suppository and the type of release media did affect drug release. It was found that drug release was sustained and diffusion-controlled in the three drugs. And finally, curdlan can be applicable for use in a sustained release suppository.

  6. [A study of 31 terminally ill cancer patients who received pure oxycodone injections at home].

    PubMed

    Sasaki, Tsubasa; Kawagoe, Izumi

    2014-11-01

    Since the launch of pure oxycodone injections in May 2012, it has been possible to use oxycodone without opioid rotation. Although an extremely important step showing progress, very few studies regarding the use of pure oxycodone injections have been performed. In this study, we evaluated the safety and efficacy of pure oxycodone injections in 31 terminally ill cancer patients receiving home care. The difficulty in oral oxycodone intake was the main reason for changing to pure oxycodone injections. The mean administered period of subcutaneous pure oxycodone was 5.6 ± 6.7 days. One out of 5 patients receiving pure oxycodone injections complained of worsening sleepiness. However, other symptoms improved. In addition, in cases wherein pure oxycodone injection was the initiating opioid, 1 out of 6 patients showed no improvement of respiratory discomfort, while other symptoms improved. It was difficult to evaluate more patients because of the short period for administration. Although 5 patients experienced skin problems, they were successfully managed by changing the injection site. Of these 5 patients, 2 patients had sensitive skin, with a previous history of alcohol rash. In conclusion, our study suggests that pure oxycodone injections are beneficial over oral oxycodone treatment for terminally ill cancer patients. However, further evaluation of skin problems associated with pure oxycodone injections is required by performing larger studies.

  7. A fatal drug interaction between oxycodone and clonazepam.

    PubMed

    Burrows, David L; Hagardorn, Andrea N; Harlan, Gretel C; Wallen, Ellen D B; Ferslew, Kenneth E

    2003-05-01

    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

  8. Modified glasgow prognostic score predicting high conversion ratio in opioid switching from oral oxycodone to transdermal fentanyl in patients with cancer pain

    PubMed Central

    Jia, Shu-Shan; Shang, Li; Li, Ming-E; Zhao, Dong-Mei; Xu, Wen-Hua; Wang, Yao-Qi

    2015-01-01

    The aim of this study was to identify predictive factors for higher conversion ratio in opioid switching from oral oxycodone to transdermal fentanyl (TDF) in patients with cancer pain. The participants of this study were 156 hospitalized cancer patients who underwent opioid switching from oral oxycodone to TDF at the Affiliated Hospital of Binzhou Medical University between January 1st, 2010 and March 31st, 2014. Patient characteristics, modified Glasgow Prognostic Score (mGPS), daily oxycodone dose, and reasons for opioid switching were retrospectively collected. The effect of variables on the conversion ratio was analyzed by multiple regression analysis to identify the predictive factors for higher conversion ratio in opioid switching from oral oxycodone to TDF. The results showed that the mGPS (odds ratio [OR], 2.358; 95% CI 1.379-4.031; P = 0.002), the reason for opioid switching (OR, 0.497; 95% CI, 0.298-0.828; P = 0.007) and equivalent oral morphine dose (OR, 1.700; 95% CI, 1.008-2.867; P = 0.046) were found to be significant predictors requiring higher conversion ratio in opioid switching. This study indicates that higher mGPS, poor pain control before switching and higher equivalent oral morphine dose are significant predictors of a need for higher conversion ratio in opioid switching from oral oxycodone to TDF. These results could contribute to the establishment of evidence-based medicine in cancer pain relief. PMID:26221306

  9. Molecularly imprinted nanotubes for enantioselective drug delivery and controlled release.

    PubMed

    Yin, Junfa; Cui, Yue; Yang, Gengliang; Wang, Hailin

    2010-11-07

    Molecularly imprinted nanotubes for enantioselective drug delivery and controlled release are fabricated by the combination of template synthesis and ATRP grafting. The release of R-propranolol from the imprinted nanotubes in rats is restricted while the release of pharmacologically active S-enantiomer is greatly promoted.

  10. Tailoring nanoarchitectonics to control the release profile of payloads

    NASA Astrophysics Data System (ADS)

    Jiang, Shuai; Lv, Liping; Li, Qifeng; Wang, Junwei; Landfester, Katharina; Crespy, Daniel

    2016-06-01

    We demonstrate here that the control over the release rate of payloads and on the selectivity of the release can be achieved by designing nanomaterials with a hierarchical structure. Redox-responsive silica nanocapsules are first synthesized to allow for an accelerated release of the corrosion inhibitor 2-mercaptobenzothiazole as a payload upon chemical reduction and retarded release upon oxidation. In a second step, we embedded the nanocapsules into nanofibers by colloid-electrospinning, yielding a hierarchical composite structure. Remarkably, the encapsulation of the nanocapsules in the fibers provides two decisive advantages that are a higher selectivity of the release and a higher control over the release rate of payloads.We demonstrate here that the control over the release rate of payloads and on the selectivity of the release can be achieved by designing nanomaterials with a hierarchical structure. Redox-responsive silica nanocapsules are first synthesized to allow for an accelerated release of the corrosion inhibitor 2-mercaptobenzothiazole as a payload upon chemical reduction and retarded release upon oxidation. In a second step, we embedded the nanocapsules into nanofibers by colloid-electrospinning, yielding a hierarchical composite structure. Remarkably, the encapsulation of the nanocapsules in the fibers provides two decisive advantages that are a higher selectivity of the release and a higher control over the release rate of payloads. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00917d

  11. Analytical solution of diffusion model for nutrient release from controlled release fertilizer

    NASA Astrophysics Data System (ADS)

    Ameenuddin Irfan, Sayed; Razali, Radzuan; KuShaari, KuZilati; Mansor, Nurlidia; Azeem, Babar

    2017-09-01

    An analytical method has been developed to solve the initial value problem which arises from Fick’s diffusion equation encountered in the modelling of the Controlled Release Fertilizers. The proposed analytical solution is developed using the modified Adomian decomposition method. This method does not require the discretization method, reliability and efficiency of this method is more and it also reduces the calculation time. The model has predicted the effect of granule radius and diffusion coefficient on the nutrient release and total release time of Controlled Release Fertilizer. Model has predicted that increase in the radius of granule reduces the release and vice versa in case of diffusion coefficient. Detailed understanding of these parameters helps in improved designing of Controlled Release Fertilizer.

  12. 28 CFR 541.50 - Release from a control unit.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Release from a control unit. 541.50 Section 541.50 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Control Unit Programs § 541.50 Release from a control unit...

  13. [Nutrient release characteristics and use efficiency of slow- and controlled release fertilizers].

    PubMed

    Duan, Lu-Lu; Zhang, Min; Liu, Gang; Shang, Zhao-Cong; Yang, Yi

    2009-05-01

    Water extraction method and soil incubation method were used to study the nutrient release characteristics of four slow- and controlled release fertilizers (CRF1, CRF2, SCU, and IBDU), and pot experiment was conducted to assess the effects of the release characteristics on the nutrient requirements of canola (Brassica napus L.). The nutrient release curves of test fertilizers in water were S pattern for CRF1 and CRF2, burst pattern for SCU, and reverse L pattern for IBDU. The nutrient release characteristics of the four fertilizers in water and in soil all fitted binomial equations, suggesting that there existed some similarities in the nutrient release in the two media. The nutrient uptake and biomass of canola plants treated with CRF1 and CRF2 were significantly higher than those treated with SCU and IBDU, and CRF2 had the greatest effect. The nutrient release curves of CRF1 and CRF2 accorded more closely with the nutrient requirements of canola.

  14. Design and study of lamivudine oral controlled release tablets.

    PubMed

    Ravi, Punna Rao; Ganga, Sindhura; Saha, Ranendra Narayan

    2007-12-07

    The objective of this study was to design oral controlled release matrix tablets of lamivudine using hydroxypropyl methylcellulose (HPMC) as the retardant polymer and to study the effect of various formulation factors such as polymer proportion, polymer viscosity, and compression force on the in vitro release of drug. In vitro release studies were performed using US Pharmacopeia type 1 apparatus (basket method) in 900 mL of pH 6.8 phosphate buffer at 100 rpm. The release kinetics were analyzed using the zero-order model equation, Higuchi's square-root equation, and the Ritger-Peppas empirical equation. Compatibility of the drug with various excipients was studied. In vitro release studies revealed that the release rate decreased with increase in polymer proportion and viscosity grade. Increase in compression force was found to decrease the rate of drug release. Matrix tablets containing 60% HPMC 4000 cps were found to show good initial release (26% in first hour) and extended the release up to 16 hours. Matrix tablets containing 80% HPMC 4000 cps and 60% HPMC 15,000 cps showed a first-hour release of 22% but extended the release up to 20 hours. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets was dependent on drug diffusion and polymer relaxation and therefore followed non-Fickian or anomalous release. No incompatibility was observed between the drug and excipients used in the formulation of matrix tablets. The developed controlled release matrix tablets of lamivudine, with good initial release (20%-25% in first hour) and extension of release up to 16 to 20 hours, can overcome the disadvantages of conventional tablets of lamivudine.

  15. Controlled release of sirolimus from a multilayered PLGA stent matrix.

    PubMed

    Wang, Xintong; Venkatraman, Subbu S; Boey, Freddy Y C; Loo, Joachim S C; Tan, Lay Poh

    2006-11-01

    The release of sirolimus from a bi-layer biodegradable polymeric film is reported in this study. Approved drug-eluting metal stents use a thin polymer coating to control drug release, but the degree of control is limited. In a fully polymeric stent, the use of multilayers allows a range of release kinetics. A bi-layer system, with PLLA as the supporting layer and PLGA as the drug-eluting layer, was used in this study to simulate release of sirolimus from a stent. The results show that the release of sirolimus is diffusion and degradation-controlled, and that the amount of sirolimus loading does not affect its release kinetics. The release of sirolimus is, however, accelerated by the addition of a plasticizer, such as PEG, as water uptake is increased. An increased water uptake increases polymer degradation, and changes the dominant mode of release to degradation-control. The release of sirolimus can, on the other hand, be retarded by using a coating of a biodegradable polyester with a lauryl ester end group. Therefore, multilayered systems offer many options for controlling sirolimus release over months.

  16. Environmental Release Prevention and Control Plan

    SciTech Connect

    Mamatey, A.; Arnett, M.

    1997-10-01

    During the history of SRS, continual improvements in facilities, process, and operations, and changes in the site`s mission have reduced the amount of radioactive liquid releases. In the early years of SRS (1958 to 1965), the amount of tritium discharged to the Savannah River averaged approximately 61,000 curies a year. During the mid-1980`s (1983 to 1988), liquid releases of tritium averaged 27,000 curies a year. By 1996, liquid releases of tritium are projected to be just 3000 curies for the year. This large projected decrease is the result of the planned shut-down of all reactors and the anticipated significant decline in the amount of tritium migrating from the site seepage basins and the Solid Waste Disposal Facility.

  17. Choice between delayed food and immediate oxycodone in rats.

    PubMed

    Secci, Maria E; Factor, Julie A; Schindler, Charles W; Panlilio, Leigh V

    2016-12-01

    The choice to seek immediate drug effects instead of more meaningful but delayed rewards is a defining feature of addiction. To develop a rodent model of this behavior, we allowed rats to choose between immediate intravenous delivery of the prescription opioid oxycodone (50 μg/kg) and delayed delivery of palatable food pellets. Rats preferred food at delays up to 30 s, but they chose oxycodone and food equally at 60-s delay and preferred oxycodone over food at 120-s delay. Comparison of food-drug choice, food-only, and drug-only conditions indicated that food availability decreased drug intake, but drug availability increased food intake. In the food-only condition, food was effective as a reinforcer even when delayed by 120 s. Pre-session feeding with chow slowed acquisition of food and drug self-administration, but did not affect choice. To establish procedures for testing potential anti-addiction medications, noncontingent pre-treatment with oxycodone or naltrexone (analogous to substitution and antagonist therapies, respectively) were tested on a baseline in which oxycodone was preferred over delayed food. Naltrexone pre-treatment decreased drug intake and increased food intake. Oxycodone pre-treatment decreased drug intake, but also produced extended periods with no food or drug responding. These findings show that the contingencies that induce preference for drugs over more meaningful but less immediate rewards in humans can be modeled in rodents, and they suggest that the model could be useful for assessing the therapeutic potential of treatments and exploring the underlying behavioral and neural mechanisms involved in addiction.

  18. Nutrient Sensing Overrides Somatostatin and Growth Hormone-Releasing Hormone to Control Pulsatile Growth Hormone Release.

    PubMed

    Steyn, F J

    2015-07-01

    Pharmacological studies reveal that interactions between hypothalamic inhibitory somatostatin and stimulatory growth hormone-releasing hormone (GHRH) govern pulsatile GH release. However, in vivo analysis of somatostatin and GHRH release into the pituitary portal vasculature and peripheral GH output demonstrates that the withdrawal of somatostatin or the appearance of GHRH into pituitary portal blood does not reliably dictate GH release. Consequently, additional intermediates acting at the level of the hypothalamus and within the anterior pituitary gland are likely to contribute to the release of GH, entraining GH secretory patterns to meet physiological demand. The identification and validation of the actions of such intermediates is particularly important, given that the pattern of GH release defines several of the physiological actions of GH. This review highlights the actions of neuropeptide Y in regulating GH release. It is acknowledged that pulsatile GH release may not occur selectively in response to hypothalamic control of pituitary function. As such, interactions between somatotroph networks, the median eminence and pituitary microvasculature and blood flow, and the emerging role of tanycytes and pericytes as critical regulators of pulsatility are considered. It is argued that collective interactions between the hypothalamus, the median eminence and pituitary vasculature, and structural components within the pituitary gland dictate somatotroph function and thereby pulsatile GH release. These interactions may override hypothalamic somatostatin and GHRH-mediated GH release, and modify pulsatile GH release relative to the peripheral glucose supply, and thereby physiological demand.

  19. The Addiction Potential of Oxycodone (Percodan®)

    PubMed Central

    Bloomquist, Edward R.

    1963-01-01

    Dihydrohydroxycodeinone (oxycodone, Percodan®) is a useful analgesic. Its addiction potential, however, is comparable to that of morphine. This fact should be considered when it is prescribed. Because of increasing numbers of addicts to this drug in the State of California, the California Medical Association Committee on Dangerous Drugs and the House of Delegates has recommended that oxycodone-containing drugs be returned to the triplicate prescription list as they were originally in 1949. This recommendation was incorporated in Senate Bill 385, which failed to pass the legislature. PMID:13971810

  20. Overview study of LNG release prevention and control systems

    SciTech Connect

    Pelto, P.J.; Baker, E.G.; Holter, G.M.; Powers, T.B.

    1982-03-01

    The liquefied natural gas (LNG) industry employs a variety of release prevention and control techniques to reduce the likelihood and the consequences of accidental LNG releases. A study of the effectiveness of these release prevention and control systems is being performed. Reference descriptions for the basic types of LNG facilities were developed. Then an overview study was performed to identify areas that merit subsequent and more detailed analyses. The specific objectives were to characterize the LNG facilities of interest and their release prevention and control systems, identify possible weak links and research needs, and provide an analytical framework for subsequent detailed analyses. The LNG facilities analyzed include a reference export terminal, marine vessel, import terminal, peakshaving facility, truck tanker, and satellite facility. A reference description for these facilities, a preliminary hazards analysis (PHA), and a list of representative release scenarios are included. The reference facility descriptions outline basic process flows, plant layouts, and safety features. The PHA identifies the important release prevention operations. Representative release scenarios provide a format for discussing potential initiating events, effects of the release prevention and control systems, information needs, and potential design changes. These scenarios range from relatively frequent but low consequence releases to unlikely but large releases and are the principal basis for the next stage of analysis.

  1. Controlled release of biologically active silver from nanosilver surfaces.

    PubMed

    Liu, Jingyu; Sonshine, David A; Shervani, Saira; Hurt, Robert H

    2010-11-23

    Major pathways in the antibacterial activity and eukaryotic toxicity of nanosilver involve the silver cation and its soluble complexes, which are well established thiol toxicants. Through these pathways, nanosilver behaves in analogy to a drug delivery system, in which the particle contains a concentrated inventory of an active species, the ion, which is transported to and released near biological target sites. Although the importance of silver ion in the biological response to nanosilver is widely recognized, the drug delivery paradigm has not been well developed for this system, and there is significant potential to improve nanosilver technologies through controlled release formulations. This article applies elements of the drug delivery paradigm to nanosilver dissolution and presents a systematic study of chemical concepts for controlled release. After presenting thermodynamic calculations of silver species partitioning in biological media, the rates of oxidative silver dissolution are measured for nanoparticles and macroscopic foils and used to derive unified area-based release kinetics. A variety of competing chemical approaches are demonstrated for controlling the ion release rate over 4 orders of magnitude. Release can be systematically slowed by thiol and citrate ligand binding, formation of sulfidic coatings, or the scavenging of peroxy-intermediates. Release can be accelerated by preoxidation or particle size reduction, while polymer coatings with complexation sites alter the release profile by storing and releasing inventories of surface-bound silver. Finally, the ability to tune biological activity is demonstrated through a bacterial inhibition zone assay carried out on selected formulations of controlled release nanosilver.

  2. Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats

    PubMed Central

    Pravetoni, M; Raleigh, MD; Le Naour, M; Tucker, AM; Harmon, TM; Jones, JM; Birnbaum, AK; Portoghese, PS; Pentel, PR

    2012-01-01

    Opioid conjugate vaccines have shown promise in animal models as a potential treatment for opioid addiction. Individual vaccines are quite specific and each targets only a limited number of structurally similar opioids. Since opioid users can switch or transition between opioids, we studied a bivalent immunization strategy of combining 2 vaccines that could target several of the most commonly abused opioids; heroin, oxycodone and their active metabolites. Morphine (M) and oxycodone (OXY) haptens were conjugated to keyhole limpet hemocyanin (KLH) through tetraglycine (Gly)4 linkers at the C6 position. Immunization of rats with M-KLH alone produced high titers of antibodies directed against heroin, 6-monoacetylmorphine (6-MAM) and morphine. Immunization with OXY-KLH produced high titers of antibodies against oxycodone and oxymorphone. Immunization with the bivalent vaccine produced consistently high antibody titers against both immunogens. Bivalent vaccine antibody titers against the individual immunogens were higher than with the monovalent vaccines alone owing, at least in part, to cross-reactivity of the antibodies. Administration of a single concurrent intravenous dose of 6-MAM and oxycodone to rats immunized with the bivalent vaccine increased 6-MAM, morphine and oxycodone retention in serum and reduced the distribution of 6-MAM and oxycodone to brain. Vaccine efficacy correlated with serum antibody titers for both monovalent vaccines, alone or in combination. Efficacy of the individual vaccines was not compromised by their combined use. Consistent with the enhanced titers in the bivalent group, a trend toward enhanced pharmacokinetic efficacy with the bivalent vaccine was observed. These data support the possibility of co-administering two or more opioid vaccines concurrently to target multiple abusable opioids without compromising the immunogenicity or efficacy of the individual components. PMID:22583811

  3. Co-administration of morphine and oxycodone vaccines reduces the distribution of 6-monoacetylmorphine and oxycodone to brain in rats.

    PubMed

    Pravetoni, M; Raleigh, M D; Le Naour, M; Tucker, A M; Harmon, T M; Jones, J M; Birnbaum, A K; Portoghese, P S; Pentel, P R

    2012-06-29

    Opioid conjugate vaccines have shown promise in animal models as a potential treatment for opioid addiction. Individual vaccines are quite specific and each targets only a limited number of structurally similar opioids. Since opioid users can switch or transition between opioids, we studied a bivalent immunization strategy of combining 2 vaccines that could target several of the most commonly abused opioids; heroin, oxycodone and their active metabolites. Morphine (M) and oxycodone (OXY) haptens were conjugated to keyhole limpet hemocyanin (KLH) through tetraglycine (Gly)(4) linkers at the C6 position. Immunization of rats with M-KLH alone produced high titers of antibodies directed against heroin, 6-monoacetylmorphine (6-MAM) and morphine. Immunization with OXY-KLH produced high titers of antibodies against oxycodone and oxymorphone. Immunization with the bivalent vaccine produced consistently high antibody titers against both immunogens. Bivalent vaccine antibody titers against the individual immunogens were higher than with the monovalent vaccines alone owing, at least in part, to cross-reactivity of the antibodies. Administration of a single concurrent intravenous dose of 6-MAM and oxycodone to rats immunized with the bivalent vaccine increased 6-MAM, morphine and oxycodone retention in serum and reduced the distribution of 6-MAM and oxycodone to brain. Vaccine efficacy correlated with serum antibody titers for both monovalent vaccines, alone or in combination. Efficacy of the individual vaccines was not compromised by their combined use. Consistent with the enhanced titers in the bivalent group, a trend toward enhanced pharmacokinetic efficacy with the bivalent vaccine was observed. These data support the possibility of co-administering two or more opioid vaccines concurrently to target multiple abusable opioids without compromising the immunogenicity or efficacy of the individual components.

  4. Characterizing the subjective, psychomotor, and physiological effects of oral oxycodone in non-drug-abusing volunteers.

    PubMed

    Zacny, James P; Gutierrez, Sandra

    2003-11-01

    The subjective, psychomotor, and physiological effects of a widely prescribed and abused prescription opioid, oxycodone, have not been studied in a population of non-drug-abusing people. To characterize the effects of oxycodone in non-drug-abusing volunteers. Eighteen volunteers participated in a crossover, randomized, double-blind study in which they received, all p.o., placebo, 10 mg oxycodone, 20 mg oxycodone, 30 mg oxycodone, 40 mg morphine, and 2 mg lorazepam. Measures were assessed before and for 300 min after drug administration. End-of-session and 24-h post-session measures were taken to assess residual drug effects and overall subjects' assessments of the drug effects. Subjective effects of oxycodone were dose related, with the majority of statistically significant effects limited to the two higher doses tested. Oxycodone produced a profile of subjective effects that included both pleasant and unpleasant effects. Morphine in general produced effects similar in magnitude to those of 10 mg and 20 mg oxycodone. Peak liking and drug-wanting ratings were increased by all doses of oxycodone and by morphine, and trough ratings of liking (dislike) were lower in the 20-mg and 30-mg oxycodone conditions, relative to the placebo condition. Post-session ratings of overall liking and drug wanting were not statistically significant, either at the end of the session or 24 h later. Cognitive and psychomotor impairment were obtained with the higher doses of oxycodone, but to a much lesser degree than that of lorazepam. Miosis and exophoria were increased in a dose-related manner by oxycodone. Oxycodone produced effects similar to those of other mu opioid agonists. Although oxycodone produced abuse liability-related subjective effects, it also produced unpleasant effects, a phenomenon we have observed in other opioid studies in non-drug-abusing volunteers.

  5. The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects.

    PubMed

    Pöyhiä, R; Seppälä, T; Olkkola, K T; Kalso, E

    1992-06-01

    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 (0.14 mg kg-1) and twice orally (0.28 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 0.07-0.08 l min-1. The kinetics of oxycodone were unaffected by amitriptyline. 4. The mean ratio of the AUC(0.24 h) values of unconjugated noroxycodone to oxycodone was 0.45 after i.m. oxycodone and 0.6-0.8 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.

  6. Can an immunoassay become a standard technique in detecting oxycodone and its metabolites?

    PubMed

    Abadie, Jude M; Allison, Kim H; Black, David A; Garbin, James; Saxon, Andrew J; Bankson, Daniel D

    2005-01-01

    Opiate toxicology testing is routinely performed in the hospital setting to identify abusers and/or to determine those patients who are not taking prescribed opiate analgesics such as oxycodone. Commercially available assays for opiate detection in urine have decreased sensitivity for oxycodone, which contributes to a high false-negative rate. Functioning as a beta site, our Veterans Affairs hospital evaluated a new enzyme immunoassay, DRI Oxycodone Assay, for its use in the qualitative and semiquantitative detection of oxycodone in urine. We hypothesize that an immunoassay for oxycodone with superior sensitivity and specificity, when compared to the traditional opiate assays, would reduce the need for more expensive and time-consuming confirmatory testing. We used the new liquid homogenous enzyme immunoassay to determine oxycodone results in a total of 148 urine samples from 4 different sample groups. Gas chromatography-mass spectroscopy was subsequently used to confirm the presence or absence of oxycodone (or its primary metabolite, noroxycodone). We also evaluated within-run, between-run, and linearity studies and conducted a crossover study to establish a cutoff value for oxycodone. In our patient population, we used the new DRI immunoassay to evaluate 17,069 urine samples to estimate oxycodone misuse profiles (patients not taking prescribed oxycodone or taking oxycodone without a prescription) during a 4-month period. The sensitivity and specificity of the new oxycodone immunoassay were 97.7% and 100%, respectively, at the cutoff concentration of 300 ng/mL. The assay linearity was 1,250 ng/mL, and the sensitivity was 10 ng/mL. Within-run precision and between-run coefficient of variation were 2.3% and 1.8%, respectively. None of the 15 compounds that we evaluated for interference had crossover significant enough to produce a positive oxycodone result when using 300 ng/mL as the cutoff value. None of the 17,069 oxycodone immunoassays was followed with a request

  7. Electrospinning nanofibers for controlled drug release

    NASA Astrophysics Data System (ADS)

    Banik, Indrani

    Electrospinning is the most widely studied technique for the synthesis of nanofibers. Electrospinning is considered as one of the technologies that can produce nanosized drugs incorporated in polymeric nanofibers. In vitro and in vivo studies have demonstrated that the release rates of drugs from these nanofiber formulations are enhanced compared to those from original drug substance. This technology has the potential for enhancing the oral delivery of poorly soluble drugs. The electrospun mats were made using Polycaprolactone/PCL, Poly(DL-lactide)/PDL 05 and Poly(DL-lactide-co-glycolide)/PLGA. The drugs incorporated in the electrospun fibers were 5-Fluorouracil and Rapamycin. The evidence of the drugs being embedded in the polymers was obtained by scanning electron microscopy (SEM), Raman and infrared spectroscopy. The release of 5-Fluorouracil and Rapamycin were followed by UV-VIS spectroscopy.

  8. Application of advanced polymeric materials for controlled release pesticides

    NASA Astrophysics Data System (ADS)

    Rahim, M.; Hakim, M. R.; Haris, H. M.

    2016-08-01

    The objective of this work was to study the capability of advanced polymeric material constituted by chitosan and natural rubber matrices for controlled release of pesticides (1-hydroxynaphthalene and 2-hydroxynaphthalene) in aqueous solution. The released amount of pesticides was measured spectrophotometrically from the absorbance spectra applying a standardized curve. The release of the pesticides was studied into refreshing and non-refreshing neutral aqueous media. Interestingly, formulation successfully indicated a consistent, controlled and prolonged release of pesticides over a period of 35 days.

  9. Comparison of the Risks of Shopping Behavior and Opioid Abuse Between Tapentadol and Oxycodone and Association of Shopping Behavior and Opioid Abuse

    PubMed Central

    Fife, Daniel; Kihm, Mary A.; Mastrogiovanni, Greg; Yuan, Yingli

    2014-01-01

    Objectives: This study compared the risks of opioid shopping behavior and opioid abuse between tapentadol immediate release and oxycodone immediate release and, to validate the definition of shopping, examined the association between opioid shopping and opioid abuse further. Materials and Methods: This retrospective cohort study using linked dispensing and diagnosis databases followed opioid-naive patients for development of shopping behavior and/or opioid abuse during 1 year after initial exposure to tapentadol or oxycodone. Shopping was defined by having overlapping opioid prescriptions from >1 prescriber filled at ≥3 pharmacies; abuse by having International Classification of Diseases, 9th revision diagnoses reflecting opioid abuse, addiction, or dependence. To determine their association, we cross-tabulated shopping and opioid abuse and calculated odds ratios. Risks of developing each outcome were estimated using logistic regression. Results: Among 277,401 participants initiating opioid use with tapentadol (39,524) or oxycodone (237,877), 0.6% developed shopping behavior, 0.75% developed abuse. Higher proportions of patients in the oxycodone group developed shopping behavior and abuse than in the tapentadol group (shopping: adjusted odds ratio [95% confidence interval], 0.45 [0.36-0.55]; abuse: 0.44 [0.37-0.54]). Shopping behavior and abuse were associated; of those with shopping behavior, 6.5% had abuse. Age (18 to 64 y), sex (male), prior benzodiazepine use, paying cash, and history (mood disorders, abuse of nonopioid medications, and back pain) were risk factors for developing either outcome. Discussion: Shopping behavior and abuse measure complementary, but associated, constructs, which further validates the current definition of shopping. The risk of developing either is lower among patients who initiate opioid use with tapentadol than those who initiate opioid use with oxycodone. PMID:24370606

  10. Comparison of the risks of shopping behavior and opioid abuse between tapentadol and oxycodone and association of shopping behavior and opioid abuse.

    PubMed

    Cepeda, M Soledad; Fife, Daniel; Kihm, Mary A; Mastrogiovanni, Greg; Yuan, Yingli

    2014-12-01

    This study compared the risks of opioid shopping behavior and opioid abuse between tapentadol immediate release and oxycodone immediate release and, to validate the definition of shopping, examined the association between opioid shopping and opioid abuse further. This retrospective cohort study using linked dispensing and diagnosis databases followed opioid-naive patients for development of shopping behavior and/or opioid abuse during 1 year after initial exposure to tapentadol or oxycodone. Shopping was defined by having overlapping opioid prescriptions from >1 prescriber filled at ≥3 pharmacies; abuse by having International Classification of Diseases, 9th revision diagnoses reflecting opioid abuse, addiction, or dependence. To determine their association, we cross-tabulated shopping and opioid abuse and calculated odds ratios. Risks of developing each outcome were estimated using logistic regression. Among 277,401 participants initiating opioid use with tapentadol (39,524) or oxycodone (237,877), 0.6% developed shopping behavior, 0.75% developed abuse. Higher proportions of patients in the oxycodone group developed shopping behavior and abuse than in the tapentadol group (shopping: adjusted odds ratio [95% confidence interval], 0.45 [0.36-0.55]; abuse: 0.44 [0.37-0.54]). Shopping behavior and abuse were associated; of those with shopping behavior, 6.5% had abuse. Age (18 to 64 y), sex (male), prior benzodiazepine use, paying cash, and history (mood disorders, abuse of nonopioid medications, and back pain) were risk factors for developing either outcome. Shopping behavior and abuse measure complementary, but associated, constructs, which further validates the current definition of shopping. The risk of developing either is lower among patients who initiate opioid use with tapentadol than those who initiate opioid use with oxycodone.

  11. Release and control of hydrogen sulfide during sludge thermal drying

    SciTech Connect

    Weng, Huanxin; Dai, Zhixin; Ji, Zhongqiang; Gao, Caixia; Liu, Chongxuan

    2015-04-15

    The release of hydrogen sulfide (H2S) during sludge drying is a major environmental problem because of its toxicity to human health. A series of experiments were performed to investigate the mechanisms and factors controlling the H2S release. Results of this study show that: 1) the biomass and activity of sulfate-reducing bacteria (SRB) in sludge were the major factors controlling the amount of H2S release, 2) the sludge drying temperature had an important effect on both the extent and the timing of H2S release from the sludge, and 3) decreasing sludge pH increased the H2S release. Based on the findings from this study, a new system that integrates sludge drying and H2S gas treatment was developed to reduce the amount of H2S released from sludge treatments.

  12. Fentanyl tolerance in the treatment of cancer pain: a case of successful opioid switching from fentanyl to oxycodone at a reduced equivalent dose.

    PubMed

    Sutou, Ichiro; Nakatani, Toshihiko; Hashimoto, Tatsuya; Saito, Yoji

    2015-06-01

    Opioids are not generally deemed to have an analgesic ceiling effect on cancer pain. However, there have been occasional reports of tolerance to opioid development induced by multiple doses of fentanyl. The authors report a case of suspected tolerance to the analgesic effect of opioid, in which an increasing dose of fentanyl failed to relieve the patient's cancer pain symptoms, but opioid switching to oxycodone injections enabled a dose reduction to below the equivalent dose conversion ratio. The patient was a 60-year-old man diagnosed with pancreatic body carcinoma with multiple metastases. The base dose consisted of 12 mg/day of transdermal fentanyl patches (equivalent to 3.6 mg/day, 150 μg/h fentanyl injection), and rescue therapy consisted of 10 mg immediate-release oxycodone powders. Despite the total daily dose of fentanyl reaching 5.6 mg (equivalent to 560 mg oral morphine), the analgesic effect was inadequate; thus, an urgent adjustment was necessary. Due to the moderate dose of fentanyl, the switch to oxycodone injection was done incrementally at a daily dose equivalent to 25% of the fentanyl injection. The total dose of oxycodone was replaced approximately 53.5% of the dose of fentanyl prior to opioid switching.

  13. Impact of morphine, fentanyl, oxycodone or codeine on patient consciousness, appetite and thirst when used to treat cancer pain.

    PubMed

    Wiffen, Philip J; Derry, Sheena; Moore, R Andrew

    2014-05-29

    There is increasing focus on providing high quality care for people at the end of life, irrespective of disease or cause, and in all settings. In the last ten years the use of care pathways to aid those treating patients at the end of life has become common worldwide. The use of the Liverpool Care Pathway in the UK has been criticised. In England the LCP was the subject of an independent review, commissioned by a Health Minister. The Neuberger Review acknowledged that the LCP was based on the sound ethical principles that provide the basis of good quality care for patients and families when implemented properly. It also found that the LCP often was not implemented properly, and had instead become a barrier to good care; it made over 40 recommendations, including education and training, research and development, access to specialist palliative care services, and the need to ensure care and compassion for all dying patients. In July 2013, the Department of Health released a statement that stated the use of the LCP should be "phased out over the next 6-12 months and replaced with an individual approach to end of life care for each patient".The impact of opioids was a particular concern because of their potential influence on consciousness, appetite and thirst in people near the end of life. There was concern that impaired patient consciousness may lead to an earlier death, and that effects of opioids on appetite and thirst may result in unnecessary suffering. This rapid review, commissioned by the National Institute for Health Research, used standard Cochrane methodology to examine adverse effects of morphine, fentanyl, oxycodone, and codeine in cancer pain studies as a close approximation to possible effects in the dying patient. To determine the impact of opioid treatment on patient consciousness, appetite and thirst in randomised controlled trials of morphine, fentanyl, oxycodone or codeine for treating cancer pain. We assessed adverse event data reported in

  14. Diffuse-interface theory for structure formation and release behavior in controlled drug release systems.

    PubMed

    Saylor, David M; Kim, Chang-Soo; Patwardhan, Dinesh V; Warren, James A

    2007-11-01

    A common method of controlling drug release has been to incorporate the drug into a polymer matrix, thereby creating a diffusion barrier that slows the rate of drug release. It has been demonstrated that the internal microstructure of these drug-polymer composites can significantly impact the drug release rate. However, the effect of processing conditions during manufacture on the composite structure and the subsequent effects on release behavior are not well understood. We have developed a diffuse-interface theory for microstructure evolution that is based on interactions between drug, polymer and solvent species, all of which may be present in either crystalline or amorphous states. Because the theory can be applied to almost any specific combination of material species and over a wide range of environmental conditions, it can be used to elucidate and quantify the relationships between processing, microstructure and release response in controlled drug release systems. Calculations based on the theory have now demonstrated that, for a characteristic delivery system, variations in microstructure arising due to changes in either drug loading or processing time, i.e. evaporation rate, could have a significant impact on both the bulk release kinetics and the uniformity of release across the system. In fact, we observed that changes in process time alone can induce differences in bulk release of almost a factor of two and typical non-uniformities of +/-30% during the initial periods of release. Because these substantial variations may have deleterious clinical ramifications, it is critical that both the system microstructure and the control of that microstructure are considered to ensure the device will be both safe and effective in clinical use.

  15. Preparation, characterization and optimization of glipizide controlled release nanoparticles

    PubMed Central

    Emami, J.; Boushehri, M.S. Shetab; Varshosaz, J.

    2014-01-01

    The purpose of the present study was to develop glipizide controlled release nanoparticles using alginate and chitosan thorough ionotropic controlled gelation method. Glipizide is a frequently prescribed second generation sulfonylurea which lowers the blood glucose in type-two diabetics. Quick absorption of the drug from the gastrointestinal tract along with short half- life of elimination makes it a good candidate for controlled release formulations. Alginate-chitosan nanoparticles (ACNP) are convenient controlled delivery systems for glipizide, due to both the release limiting properties of the system, and the bioadhesive nature of the polymers. In the present study, glipizide loaded alginate-chitosan nanoparticles (GlACNP) were prepared, and the particle characteristics including particle size (PS), zeta potential (ZP), entrapment efficiency (EE%), loading percent (LP), and mean release time (MRT), as well as the morphology of the nanoparticles, the drug-excipient compatibility, and the release kinetics along with the drug diffusion mechanism were evaluated. The results suggested that ionotropic controlled gelation method offers the possibility of preparing the nanoparticles in mild conditions in an aqueous environment, and can lead to the preparation of particles with favorable size, controlled release characteristics, and high entrapment efficiency, serving as a convenient delivery system for glipizide. The particle and release characteristics can be efficiently optimized using the Box-Behnken design. Based on the findings of the present study, it is expected that this novel formulation be a superior therapeutic alternative to the currently available glipizide delivery systems. PMID:25657802

  16. Best Practices for Controlling Lead and Copper Release

    EPA Science Inventory

    Presentation draft, covering summary of current state-of-the-art knowledge for the best treatment strategies for minimizing lead release and controlling copper release. The presentation is intended to aid with compliance with the Lead and Copper Rule, but also provide a guide to...

  17. Best Practices for Controlling Lead and Copper Release

    EPA Science Inventory

    Presentation draft, covering summary of current state-of-the-art knowledge for the best treatment strategies for minimizing lead release and controlling copper release. The presentation is intended to aid with compliance with the Lead and Copper Rule, but also provide a guide to...

  18. Metabolism of Oxycodone in Human Hepatocytes from Different Age Groups and Prediction of Hepatic Plasma Clearance

    PubMed Central

    Korjamo, Timo; Tolonen, Ari; Ranta, Veli-Pekka; Turpeinen, Miia; Kokki, Hannu

    2012-01-01

    Oxycodone is commonly used to treat severe pain in adults and children. It is extensively metabolized in the liver in adults, but the maturation of metabolism is not well understood. Our aim was to study the metabolism of oxycodone in cryopreserved human hepatocytes from different age groups (3 days, 2 and 5 months, 4 years, adult pool) and predict hepatic plasma clearance of oxycodone using these data. Oxycodone (0.1, 1, and 10 μM) was incubated with hepatocytes for 4 h, and 1 μM oxycodone also with CYP3A inhibitor ketoconazole (1 μM). Oxycodone and noroxycodone concentrations were determined at several time points with liquid chromatography–mass spectrometry. In vitro clearance of oxycodone was used to predict hepatic plasma clearance, using the well-stirred model and published physiological parameters. Noroxycodone was the major metabolite in all batches and ketoconazole inhibited the metabolism markedly in most cases. A clear correlation between in vitro oxycodone clearance and CYP3A4 activity was observed. The predicted hepatic plasma clearances were typically much lower than the published median total plasma clearance from pharmacokinetic studies. The data suggests that there are no children-specific metabolites of oxycodone. Moreover, CYP3A activity seems to be the major determinant in metabolic clearance of oxycodone regardless of age group or individual variability in hepatocyte batches. PMID:22291644

  19. Ethanol Reversal of Tolerance to the Antinociceptive Effects of Oxycodone and Hydrocodone.

    PubMed

    Jacob, Joanna C; Poklis, Justin L; Akbarali, Hamid I; Henderson, Graeme; Dewey, William L

    2017-07-01

    This study compared the development of tolerance to two orally bioavailable prescription opioids, oxycodone and hydrocodone, to that of morphine, and the reversal of this tolerance by ethanol. Oxycodone (s.c.) was significantly more potent in the mouse tail-withdrawal assay than either morphine or hydrocodone. Oxycodone was also significantly more potent in this assay than hydrocodone when administered orally. Tolerance was seen following chronic subcutaneous administration of each of the three drugs and by the chronic administration of oral oxycodone, but not following the chronic oral administration of hydrocodone. Ethanol (1 g/kg i.p.) significantly reversed the tolerance to the subcutaneous administration of each of the three opioids that developed when given 30 minutes prior to challenge doses. It took twice as much ethanol, when given orally, to reverse the tolerance to oxycodone. We investigated whether the observed tolerance to oxycodone and its reversal by ethanol were due to biodispositional changes or reflected a true neuronal tolerance. As expected, a relationship between brain oxycodone concentrations and activity in the tail-immersion test existed following administration of acute oral oxycodone. Following chronic treatment, brain oxycodone concentrations were significantly lower than acute concentrations. Oral ethanol (2 g/kg) reversed the tolerance to chronic oxycodone, but did not alter brain concentrations of either acute or chronic oxycodone. These studies show that there is a metabolic component of tolerance to oxycodone; however, the reversal of that tolerance by ethanol is not due to an alteration of the biodisposition of oxycodone, but rather is neuronal in nature. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  20. Investigation of excipient type and level on drug release from controlled release tablets containing HPMC.

    PubMed

    Williams, Robert O; Reynolds, Thomas D; Cabelka, Tim D; Sykora, Matthew A; Mahaguna, Vorapann

    2002-05-01

    The purpose of this study was to investigate the influence of excipient type and level on the release of alprazolam formulated in controlled release matrix tablets containing hydroxypropyl methylcellulose (HPMC). Each tablet formulation contained alprazolam, HPMC (Methocel K4MP), excipients, and magnesium stearate. The soluble excipients investigated were lactose monohydrate, sucrose, and dextrose, and the insoluble excipients included dicalcium phosphate dihydrate, dicalcium phosphate anhydrous, and calcium sulfate dihydrate. The similarity factor (f2 factor) was used to compare the dissolution profile of each formulation. The insoluble excipients, especially dicalcium phosphate dihydrate, caused the drug to be released at a slower rate and to a lesser extent than the soluble excipients. Soluble excipients created a more permeable hydrated gel layer for drug release, increased the porosity resulting in faster diffusion of drug, and increased the rate of tablet erosion. Use of binary mixtures of lactose monohydrate and dicalcium phosphate dihydrate produced release profiles of intermediate duration. Rapid drug dissolution was obtained when only 9.1% w/w of lactose monohydrate was present in the tablet formulation. Only when the dicalcium phosphate dihydrate level was sufficiently high (36.5% w/w) was the release rate and extent decreased. It was demonstrated that the type and level of excipient influenced the rate and extent of drug release from controlled release tablets containing HPMC. The release mechanism of alprazolam from each tablet formulation was described by either the Hixson-Crowell cube root kinetics equation or Peppas's equation. However, the different excipient types investigated did not influence the release mechanism of alprazolam from the final tablets.

  1. Nanostructured Hybrid Materials for Controlled Energy Release

    DTIC Science & Technology

    2014-06-10

    a carbon nanofiber matrix in order to control the reactivity of the aluminum nanoparticles. We achieved nanohybrid materials of aluminum...nanoparticles wrapped with Carbon nanofibers (CNFs) by electrospinning method. The morphology of aluminum decorated carbonized CNFs were studied by...to a carbon nanofiber matrix in order to control the reactivity of the aluminum nanoparticles. We achieved nanohybrid materials of aluminum

  2. Photoresponsive lipid-polymer hybrid nanoparticles for controlled doxorubicin release

    NASA Astrophysics Data System (ADS)

    Yao, Cuiping; Wu, Ming; Zhang, Cecheng; Lin, Xinyi; Wei, Zuwu; Zheng, Youshi; Zhang, Da; Zhang, Zhenxi; Liu, Xiaolong

    2017-06-01

    Currently, photoresponsive nanomaterials are particularly attractive due to their spatial and temporal controlled drug release abilities. In this work, we report a photoresponsive lipid-polymer hybrid nanoparticle for remote controlled delivery of anticancer drugs. This hybrid nanoparticle comprises three distinct functional components: (i) a poly(D,L-lactide-co-glycolide) (PLGA) core to encapsulate doxorubicin; (ii) a soybean lecithin monolayer at the interface of the core and shell to act as a molecular fence to prevent drug leakage; (iii) a photoresponsive polymeric shell with anti-biofouling properties to enhance nanoparticle stability, which could be detached from the nanoparticle to trigger the drug release via a decrease in the nanoparticle’s stability under light irradiation. In vitro results revealed that this core-shell nanoparticle had excellent light-controlled drug release behavior (76% release with light irradiation versus 10% release without light irradiation). The confocal microscopy and flow cytometry results also further demonstrated the light-controlled drug release behavior inside the cancer cells. Furthermore, a CCK8 assay demonstrated that light irradiation could significantly improve the efficiency of killing cancer cells. Meanwhile, whole-animal fluorescence imaging of a tumor-bearing mouse also confirmed that light irradiation could trigger drug release in vivo. Taken together, our data suggested that a hybrid nanoparticle could be a novel light controlled drug delivery system for cancer therapy.

  3. Controlled Release of Imidacloprid from Poly Styrene-Diacetone - Nanoformulation

    NASA Astrophysics Data System (ADS)

    Qian, Kun; Guo, Yanzhen; He, Lin

    2012-01-01

    Imidacloprid is a neonicotinoids insecticide, which is important for the cash crops such as tomato, rape and so on. The conventional formulation does not only increase the loss of pesticide but also leads to environmental pollution. Controlled-release formulations of pesticide are highly desirable not only for attaining the most effective utilization of the pesticide, but also for reducing environmental pollution. Pesticide imidacloprid was incorporated in poly (styrene-diacetone crylamide)-based formulation to obtain controlled release properties, and the imidacloprid nanocontrolled release formulation was characterized by infrared (IR) and field emission scanning electron microscope (FESEM). Factors related to loading efficiency, swelling and release behaviors of the formulation were investigated. It showed that the loading efficiency could reach about 40% (w/w). The values for the diffusion exponent "n" were in the range of 0.31-0.58, which indicated that the release of imidacloprid was diffusion-controlled. The time taken for 50% of the active ingredient to be released into water, T50, was also calculated for the comparison of formulations in different conditions. The results showed that the formulation with higher temperature and more diacetone crylamide had lower value of T50, which means a quicker release of the active ingredient. This study highlighted some pieces of evidence that improved pesticide incorporation and slower release were linked to potential interactions between the pesticide and the polymer.

  4. Trigger release liposome systems: local and remote controlled delivery?

    PubMed

    Bibi, Sagida; Lattmann, E; Mohammed, Afzal R; Perrie, Yvonne

    2012-01-01

    Target-specific delivery has become an integral area of research in order to increase bioavailability and reduce the toxic effects of drugs. As a drug-delivery option, trigger-release liposomes offer sophisticated targeting and greater control-release capabilities. These are broadly divided into two categories; those that utilise the local environment of the target site where there may be an upregulation in certain enzymes or a change in pH and those liposomes that are triggered by an external physical stimulus such as heat, ultrasound or light. These release mechanisms offer a greater degree of control over when and where the drug is released; furthermore, targeting of diseased tissue is enhanced by incorporation of target-specific components such as antibodies. This review aims to show the development of such trigger release liposome systems and the current research in this field.

  5. PREVENTION REFERENCE MANUAL: CONTROL TECHNOLOGIES, VOL. 2. POST-RELEASE MITIGATION MEASURES FOR CONTROLLING ACCIDENTAL RELEASES OF AIR TOXICS

    EPA Science Inventory

    The volume discusses prevention and protection measures for controlling accidental releases of air toxics. The probability of accidental releases depends on the extent to which deviations (in magnitude and duration) in the process can be tolerated before a loss of chemical contai...

  6. PREVENTION REFERENCE MANUAL: CONTROL TECHNOLOGIES, VOL. 2. POST-RELEASE MITIGATION MEASURES FOR CONTROLLING ACCIDENTAL RELEASES OF AIR TOXICS

    EPA Science Inventory

    The volume discusses prevention and protection measures for controlling accidental releases of air toxics. The probability of accidental releases depends on the extent to which deviations (in magnitude and duration) in the process can be tolerated before a loss of chemical contai...

  7. Controlled Release of Biologically Active Silver from Nanosilver Surfaces

    PubMed Central

    Liu, Jingyu; Sonshine, David A.; Shervani, Saira; Hurt, Robert H.

    2010-01-01

    Major pathways in the antibacterial activity and eukaryotic toxicity of nano-silver involve the silver cation and its soluble complexes, which are well established thiol toxicants. Through these pathways, nano-silver behaves in analogy to a drug delivery system, in which the particle contains a concentrated inventory of an active species, the ion, which is transported to and released near biological target sites. Although the importance of silver ion in the biological response to nano-silver is widely recognized, the drug delivery paradigm has not been well developed for this system, and there is significant potential to improve nano-silver technologies through controlled release formulations. This article applies elements of the drug delivery paradigm to nano-silver dissolution and presents a systematic study of chemical concepts for controlled release. After presenting thermodynamic calculations of silver species partitioning in biological media, the rates of oxidative silver dissolution are measured for nanoparticles and macroscopic foils and used to derive unified area-based release kinetics. A variety of competing chemical approaches are demonstrated for controlling the ion release rate over four orders of magnitude. Release can be systematically slowed by thiol and citrate ligand binding, formation of sulfidic coatings, or the scavenging of peroxy-intermediates. Release can be accelerated by pre-oxidation or particle size reduction, while polymer coatings with complexation sites alter the release profile by storing and release inventories of surface-bound silver. Finally, the ability to tune biological activity is demonstrated through bacterial inhibition zone assay carried out on selected formulations of controlled release nano-silver. PMID:20968290

  8. A controlled biochemical release device with embedded nanofluidic channels

    NASA Astrophysics Data System (ADS)

    Yang, Haifeng; Hong, Wei; Dong, Liang

    2012-04-01

    A controlled release device is developed by embedding nanofluidic biomolecule reservoirs into a polymer network of a stimuli-responsive hydrogel. The reservoirs are made of liquid core-polymer shell nanofibers using co-electrospinning. The mechanism of controlled release is based on buckling instability of the polymer shell under combined axial and radial compression, caused by volume changes of hydrogel responding to a specific stimulus. The device decouples releasable biomolecules from a hydrogel polymer matrix, avoiding chemical interactions between biomolecules and hydrogel polymer chains, and thus, alleviating nontrivial chemical and biological engineering design of hydrogel formulations. Temperature-sensitive hydrogel is used as a model hydrogel.

  9. [Drug release system controlled by near infrared light].

    PubMed

    Niidome, Takuro

    2013-01-01

    Gold nanorods have absorption bands in the near-infrared region; in this spectral range, light penetrates deeply into tissues. The absorbed light energy is converted into heat by gold nanorods. This is the so-called photothermal effect. Gold nanorods are therefore expected to act not only as thermal converters for photothermal therapy, but also as controllers for drug-release systems responding to irradiation with near-infrared light. To achieve a controlled-release system that could be triggered by light irradiation, the gold nanorods were modified with double-stranded DNA (dsDNA). When the dsDNA-modified gold nanorods were irradiated with near-infrared light, single-stranded DNA (ssDNA) was released from the gold nanorods because of the photothermal effect. The release of ssDNA was also observed in tumors grown on mice after near-infrared light irradiation. We also proposed a different controlled-release system responding to near-infrared light. Gold nanorods were modified with polyethylene glycol (PEG) through Diels-Alder cycloadducts. When the gold nanorods were irradiated with near-infrared light, the PEG chains were released from the gold nanorods because of the retro Diels-Alder reaction induced by the photothermal effect. Such controlled-release systems triggered by near-infrared light irradiation will be expanded for gold nanorod drug delivery system applications.

  10. Effects of filtration on the presence of particulate and oxycodone content of injections prepared from crushed OxyContin® tablets.

    PubMed

    Patel, Pankaj; Patel, Rahul P; Brandon, Susan; McLean, Stuart; Bruno, Raimondo; de Graaff, Barbara

    2012-07-01

    It is common for injecting drug users (IDU) to prepare injections by crushing tablets which are not designed for parental administration. The injection of insoluble tablet excipients can lead to serious local and systemic medical complications. The aim of the study was to investigate the effectiveness of various types of filters in removing harmful insoluble particles from the injections prepared using crushed oxycodone tablets. Injections were prepared from a sustained-release oxycodone tablet formulation. The filtration of tablet extracts was carried out following procedures used by IDU using makeshift filter and commercially available filters. Particulate contamination and oxycodone content were analysed using light microscopy and spectrophotometer. Unfiltered extracts contained hundreds of thousands of particles of sufficient size to cause harms. Cigarette filters removed large particles but failed to remove small particles. The combination of cigarette filter and syringe filter (0.45 μm or 0.22 μm) reduced the particle count by 90 - 95%. A double membrane syringe filter (0.8/0.2 μm) removed more than 99% of the particles. Recovery of oxycodone was more than 95% with the tested syringe filters. Particulate contamination in injections prepared from crushed tablets can be effectively removed using a combination process of cigarette filter and syringe filters, or a 0.8/0.2 μm syringe filter. Compared to other filters, the 0.8/0.2 μm syringe filter did not block, the filtration was quick and easy to perform, and did not retain oxycodone. The use of a 0.8/0.2 μm syringe filter can provide an important harm reduction measure for IDU.

  11. Modifying sorbents in controlled release formulations to prevent herbicides pollution.

    PubMed

    Flores Céspedes, F; Villafranca Sánchez, M; Pérez García, S; Fernández Pérez, M

    2007-10-01

    The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in alginate-based granules to obtain controlled release properties. In this research the effect of incorporation of sorbents such as bentonite, anthracite and activated carbon in alginate basic formulation were not only studied on encapsulation efficiency but also on the release rate of herbicides which was studied using water release kinetic tests. In addition, sorption studies of herbicides with bentonite, anthracite and activated carbon were made. The kinetic experiments of chloridazon and metribuzin release in water have shown that the release rate is higher in metribuzin systems than in those prepared with chloridazon, which has lower water solubility. Besides, it can be deduced that the use of sorbents reduces the release rate of the chloridazon and metribuzin in comparison to the technical product and to the alginate formulation without sorbents. The highest decrease in release rate corresponds to the formulations prepared with activated carbon as a sorbent. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T(50), were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the herbicide release data, the release of chloridazon and metribuzin from the various formulations into water is controlled by a diffusion mechanism. Sorption capacity of the sorbents for chloridazon and metribuzin, ranging from 0.53mgkg(-1) for the metribuzin sorption on bentonite to 2.03x10(5)mgkg(-1) for the sorption of chloridazon on the activated carbon, was the most important factor modulating the herbicide release.

  12. Controlled release implants based on cast lipid blends.

    PubMed

    Kreye, F; Siepmann, F; Zimmer, A; Willart, J F; Descamps, M; Siepmann, J

    2011-05-18

    The aim of this study was to use lipid:lipid blends as matrix formers in controlled release implants. The systems were prepared by melting and casting and thoroughly characterized before and after exposure to the release medium. Based on the experimental results, a mechanistic realistic mathematical model was used to get further insight into the underlying drug release mechanisms. Importantly, broad spectra of drug release patterns could be obtained by simply varying the lipid:lipid blend ratio in implants based on Precirol ATO 5 (glyceryl palmitostearate):Dynasan 120 (hardened soybean oil) mixtures loaded with propranolol hydrochloride. Release periods ranging from a few days up to several months could be provided. Interestingly, the drug release rate monotonically decreased with increasing Dynasan 120 content, except for implants containing about 20-25% Precirol, which exhibited surprisingly high release rates. This could be attributed to the incomplete miscibility of the two lipids at these blend ratios: DSC thermograms showed phase separation in these systems. This is likely to cause differences in the implants' microstructure, which determines the mobility of water and dissolved drug as well as the mechanical stability of the systems. Purely diffusion controlled drug release was only observed at Precirol ATO 5 contents around 5-10%. In all other cases, limited drug solubility effects or matrix former erosion are also expected to play a major role. Thus, lipid:lipid blends are very interesting matrix formers in controlled release implants. However, care must be taken with respect to the mutual miscibility of the compounds: in case of phase separation, surprisingly high drug release rates might be observed. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Modeling controlled nutrient release from polymer coated fertilizers: diffusion release from single granules.

    PubMed

    Shaviv, Avi; Raban, Smadar; Zaidel, Elina

    2003-05-15

    A comprehensive model describing the complex and "non-Fickian" (mathematically nonlinear) nature of the release from single granules of membrane coated, controlled release fertilizers (CRFs) is proposed consisting of three stages: i. a lag period during which water penetrates the coating of the granule dissolving part of the solid fertilizer in it ii. a period of linear release during which water penetration into and release out occur concomitantly while the total volume of the granules remains practically constant; and iii. a period of "decaying release", starting as the concentration inside the granule starts to decrease. A mathematical model was developed based on vapor and nutrient diffusion equations. The model predicts the release stages in terms of measurable geometrical and chemophysical parameters such as the following: the product of granule radius and coating thickness, water and solute permeability, saturation concentration of the fertilizer, and its density. The model successfully predicts the complex and "sigmoidal" pattern of release that is essential for matching plant temporal demand to ensure high agronomic and environmental effectiveness. It also lends itself to more complex statistical formulations which account for the large variability within large populations of coated CRFs and can serve for further improving CRF production and performance.

  14. Development of controlled release tablet by optimizing HPMC: consideration of theoretical release and RSM.

    PubMed

    Pani, Nihar R; Nath, Lila K

    2014-04-15

    The objective of the study was to develop controlled release tablets of nateglinide, a meglitinide derivative anti-diabetic drug, considering theoretical release profile and response surface methodology (RSM). 3(2) factorial design was utilized to optimize concentration of hydroxylpropylmethylcellulose (HPMC) K15M and K100M to obtain the desired responses (drug release at one and six hours). Theoretical release profile of drug for controlled release formulation was calculated and considered as reference for the determination of similarity factor (f2) and desimilarity factor (f1). RSM, f2 and f1 were used to select the optimum formulation. Formulation containing HPMC K15M (5%) and HPMC K100M (15%) was found optimum with desired responses with f2=86.05 and drug release profile followed zero order kinetics. Excipients used were compatible with drug, confirmed initially through DSC and IST study. The optimization of experiments was validated and optimum formulation was passed the stability study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Controlled release of tocopherols from polymer blend films

    NASA Astrophysics Data System (ADS)

    Obinata, Noe

    Controlled release packaging has great potential to increase storage stability of foods by releasing active compounds into foods continuously over time. However, a major limitation in development of this technology is the inability to control the release and provide rates useful for long term storage of foods. Better understanding of the factors affecting active compound release is needed to overcome this limitation. The objective of this research was to investigate the relationship between polymer composition, polymer processing method, polymer morphology, and release properties of active compounds, and to provide proof of principle that compound release is controlled by film morphology. A natural antioxidant, tocopherol was used as a model active compound because it is natural, effective, heat stable, and soluble in most packaging polymers. Polymer blend films were produced from combination of linear low density polyethylene (LLDPE) and high density polyethylene (HDPE), polypropylene (PP), or polystyrene (PS) with 3000 ppm mixed tocopherols using conventional blending method and innovative blending method, smart blending with a novel mixer using chaotic advection. Film morphologies were visualized with scanning electron microscopy (SEM). Release of tocopherols into 95% ethanol as a food simulant was measured by UV/Visible spectrophotometry or HPLC, and diffusivity of tocopherols in the polymers was estimated from this data. Polymer composition (blend proportions) and processing methods have major effects on film morphology. Four different types of morphologies, dispersed, co-continuous, fiber, and multilayer structures were developed by either conventional extrusion or smart blending. With smart blending of fixed polymer compositions, different morphologies were progressively developed with fixed polymer composition as the number of rod rotations increased, providing a way to separate effects of polymer composition and morphology. The different morphologies

  16. Controlled release of curcumin from poly(HEMA-MAPA) membrane.

    PubMed

    Caka, Müşerref; Türkcan, Ceren; Aktaş Uygun, Deniz; Uygun, Murat; Akgöl, Sinan; Denizli, Adil

    2017-05-01

    In this work, poly(HEMA-MAPA) membranes were prepared by UV-polymerization technique. These membranes were characterized by SEM, FTIR, and swelling studies. Synthesized membranes had high porous structure. These membranes were used for controlled release of curcumin which is already used as folk remedy and used as drug for some certain diseases and cancers. Curcumin release was investigated for various pHs and temperatures. Optimum drug release yield was found to be as 70% at pH 7.4 and 37 °C within 2 h period. Time-depended release of curcumin was also investigated and its slow release from the membrane demonstrated within 48 h.

  17. Controlled release with coating layer of permeable particles.

    PubMed

    Ito, Ryusei; Golman, Boris; Shinohara, Kunio

    2003-10-30

    An enhanced method was proposed for controlled release of core material using a coating layer of fine permeable particles dispersed in an impermeable wax prepared by dry-based process. A mathematical model was constructed to describe in detail the core material release by diffusion through the connected permeable particles inside the coating layer. The effective diffusivity was simulated by a random walk method taking into account the structure of the coating layer. The released characteristics were measured for the urea core particle coated with the layer of the starch permeable particles dispersed in the paraffin wax. The calculated results were in a good quantitative agreement with experimental data in all range of coating conditions. As a result, the low release rate was proven to be obtained with thicker coating layer of lower volume fraction of permeable particles. Moreover, the application of permeable particles instead of soluble ones [J. Chem. Eng. Jpn. 35 (2002) 40] resulted in significant decrease in release rate.

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

    PubMed

    Wolf, Barbara C; Lavezzi, Wendy A; Sullivan, Linda M; Flannagan, Lisa M

    2005-01-01

    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.

  19. Evaluating Carbon Release Rate of Controlled-release Tablet and Its Applicability to Biological Nitrate Denitrification

    NASA Astrophysics Data System (ADS)

    Yeum, Y.; HAN, K.; Yoon, J.; Lee, J.; Song, K.; Kang, J. H.; Park, C. W.; Kim, Y.

    2016-12-01

    Generally, indigenous microbes in an aquifer have known to effectively degrade nitrate through heterotrophic denitrification in the presence of carbon source (CS). However, in case of continuous injection of excess amount of CS into an aquifer for complete denitrification of nitrate to nitrogen gas, the injection of CS frequently results in biological clogging around the vicinity of an injection well. To overcome this problem, we developed a controlled-release CS tablet (CRCST) using fumarate as a CS. However, there is lack of study about CRCST release profile under field condition and its applicability to nitrate denitrification. Thus, we assessed CS release profile of CRCST in a continuous flowing cell (CFC) and its efficiency on biological denitrification in a soil column. During the CFC test, six different CRCSTs (3 for precipitating CRCSTs and 3 for floating CRCSTs) having different contents of polymer controlling CS release evaluated. CFC was operated under four different flowrates similar to groundwater velocities, and CRCST was added into the CFC before injecting test solution containing bromide (100 mg/L) as a tracer. During the soil column test, CFC and soil column was connected in sequence. Test solution containing nitrate (30 mg-N/L) and bromide was pumped into CFC, and its effluent was pumped into the column. Although the CRCSTs contain different amount of polymer, CS release rate and peak concentration of CS were highly proportional to flow rate. The ranges of CS release rate for precipitating and floating CRCSTs were 1.35-2.83 and 0.41-4.05 mmol/L/hr, respectively. The result suggests that groundwater velocity is a key parameter affecting CS release rate of CRCST. During the soil column test, one tablet addition of precipitating and floating CRCST maintained nitrate concentration less than 10mg-N/L (drinking water standard) for 4.3 and 3.7 days, respectively. These results suggest that CRCST may apply for the effective means of controlling high

  20. Controlled Release in Transdermal Pressure Sensitive Adhesives using Organosilicate Nanocomposites

    PubMed Central

    Shaikh, Sohel; Birdi, Anil; Qutubuddin, Syed; Lakatosh, Eric; Baskaran, Harihara

    2010-01-01

    Polydimethyl siloxane (PDMS) based pressure sensitive adhesives (PSA) incorporating organo-clays at different loadings were fabricated via solution casting. Partially exfoliated nanocomposites were obtained for the hydroxyl terminated PDMS in ethyl acetate solvent as determined by X-ray diffraction (XRD) and atomic force microscopy (AFM). Drug release studies showed that the initial burst release was substantially reduced and the drug release could be controlled by the addition of organo-clay. Shear strength and shear adhesion failure temperature (SAFT) measurements indicated substantial improvement in adhesive properties of the PSA nanocomposite adhesives. Shear strength showed more than 200 % improvement at the lower clay loadings and the SAFT increased by about 21% due to the reinforcement provided by the nano-dispersed clay platelets. It was found that by optimizing the level of the organosilicate additive to the polymer matrix, superior control over drug release kinetics and simultaneous improvements in adhesive properties could be attained for a transdermal PSA formulation. PMID:17786555

  1. Magnetic molecularly imprinted polymer for aspirin recognition and controlled release

    NASA Astrophysics Data System (ADS)

    Kan, Xianwen; Geng, Zhirong; Zhao, Yao; Wang, Zhilin; Zhu, Jun-Jie

    2009-04-01

    Core-shell structural magnetic molecularly imprinted polymers (magnetic MIPs) with combined properties of molecular recognition and controlled release were prepared and characterized. Magnetic MIPs were synthesized by the co-polymerization of methacrylic acid (MAA) and trimethylolpropane trimethacrylate (TRIM) around aspirin (ASP) at the surface of double-bond-functionalized Fe3O4 nanoparticles in chloroform. The obtained spherical magnetic MIPs with diameters of about 500 nm had obvious superparamagnetism and could be separated quickly by an external magnetic field. Binding experiments were carried out to evaluate the properties of magnetic MIPs and magnetic non-molecularly imprinted polymers (magnetic NIPs). The results demonstrated that the magnetic MIPs had high adsorption capacity and selectivity to ASP. Moreover, release profiles and release rate of ASP from the ASP-loaded magnetic MIPs indicated that the magnetic MIPs also had potential applications in drug controlled release.

  2. Quinine as a potential tracer for medication adherence: A pharmacokinetic and pharmacodynamic assessment of quinine alone and in combination with oxycodone in humans.

    PubMed

    Babalonis, Shanna; Hampson, Aidan J; Lofwall, Michelle R; Nuzzo, Paul A; Walsh, Sharon L

    2015-12-01

    Effective strategies to monitor pharmacotherapy adherence are necessary, and sensitive biological markers are lacking. This study examined a subtherapeutic dose of quinine as a potential adherence tracer. Primary aims included examination of the plasma and urinary pharmacokinetic profile of once-daily quinine; secondary aims assessed pharmacokinetic/pharmacodynamic interactions with oxycodone (a CYP3A and CYP2D substrate). Healthy, nondependent opioid users (n = 9) were enrolled in this within-subject, double-blind, placebo-controlled inpatient study. Participants received the following oral doses: day 1, oxycodone (30 mg); days 2-4, quinine (80 mg); day 5, quinine and oxycodone (2 hours postquinine). Blood and 24-hour urine samples were collected throughout the study, and pharmacodynamic outcomes were assessed during experimental sessions (days 1, 4, 5). Quinine displayed a plasma Tmax ∼2 hours and t1/2 ∼10 hours. Oxycodone and noroxycodone parameters (Tmax , Cmax , t1/2 ) were similar with or without quinine present, although drug exposure (AUC) was slightly greater when combined with quinine. No pharmacodynamic interactions were detected, and doses were safely tolerated. During washout, quinine urinary concentrations steadily declined (elimination t1/2 ∼16 hours), with a 94% decrease observed 72 hours postdose. Overall, low-dose quinine appears to be a good candidate for a medication additive to monitor adherence for detection of missed medication.

  3. Quinine as a potential tracer for medication adherence: A pharmacokinetic and pharmacodynamic assessment of quinine alone and in combination with oxycodone in humans

    PubMed Central

    Babalonis, Shanna; Hampson, Aidan J.; Lofwall, Michelle R.; Nuzzo, Paul A.; Walsh, Sharon L.

    2015-01-01

    Effective strategies to monitor pharmacotherapy adherence are necessary, and sensitive biological markers are lacking. This study examined a sub-therapeutic dose of quinine as a potential adherence tracer. Primary aims included examination of the plasma and urinary pharmacokinetic profile of once-daily quinine; secondary aims assessed pharmacokinetic/pharmacodynamic interactions with oxycodone (a CYP3A and CYP2D substrate). Healthy, non-dependent opioid users (n=9) were enrolled in this within-subject, double-blind, placebo-controlled, inpatient study. Participants received the following oral doses, Day 1: oxycodone (30 mg), Days 2-4: quinine (80 mg), Day 5: quinine and oxycodone (2 hrs post-quinine). Blood and 24-hr urine samples were collected throughout the study, and pharmacodynamic outcomes were assessed during experimental sessions (Days 1, 4, 5). Quinine displayed a plasma Tmax ∼2 hrs and t1/2 ∼10 hrs. Oxycodone and noroxycodone parameters (Tmax, Cmax, t1/2) were similar with or without quinine present, although drug exposure (AUC) was slightly greater when combined with quinine. No pharmacodynamic interactions were detected and doses were safely tolerated. During washout, quinine urinary concentrations steadily declined (elimination t1/2 ∼16 hrs), with a 94% decrease observed 72 hrs post-dose. Overall, low-dose quinine appears to be a good candidate for a medication additive to monitor adherence for detection of missed medication. PMID:26032168

  4. [Effects of in vitro conditions on release behavior of different types of sustained and controlled release formulations of breviscapin].

    PubMed

    He, Yan; Zeng, Xiang-Teng; Pan, Wei-San

    2008-11-01

    Insoluble breviscapin was chosen as the model drug. Bi-layer osmotic pump technology and gel matrix technology were used to prepare the breviscapin sustained and controlled release preparations. Dissimilarity factors (f1) and similarity factors (f2) were applied as similar judgment index to compare the effects of in vitro conditions on the release behavior of different types of breviscapin sustained and controlled release preparations. The tolerance of in vitro release conditions of bi-layer osmotic pump technology and gel matrix technology were studied. The results showed that in vitro release conditions have a greater impact on the gel matrix sustained release formulations, while have almost no effects on the osmotic pump controlled release formulations. Therefore, osmotic pump controlled release technology is less affected by the drug release environment. And it has a very good application prospect.

  5. Controlled release fertilizer improves quality of container longleaf pine seedlings

    Treesearch

    R. Kasten Dumroese; Jeff Parkhurst; James P. Barnett

    2005-01-01

    In an operational trial, increasing the amount of nitrogen (N) applied to container longleaf pine seedlings by incorporating controlled release fertilizer (CRF) into the media improved seedling growth and quality. Compared with control seedlings that received 40 mg N, seedlings receiving 66 mg N through CRF supplemented with liquid fertilizer had needles that were 4 in...

  6. DNA-based intelligent logic controlled release systems.

    PubMed

    Wen, Yongqiang; Xu, Liping; Li, Chuanbao; Du, Hongwu; Chen, Linfeng; Su, Bin; Zhang, Zhiliang; Zhang, Xueji; Song, Yanlin

    2012-08-28

    DNA assembles that can perform "OR" and "AND" logic gate operations were fabricated. The feasibility of intelligent logic controlled release was demonstrated through the controlled organization of gold nanoparticles on the surface of mesoporous silica by stimuli-induced structural transformation of DNA ensembles.

  7. Formulation of controlled release gellan gum macro beads of amoxicillin.

    PubMed

    Babu, R Jayachandra; Sathigari, Sateesh; Kumar, M Thilek; Pandit, J K

    2010-01-01

    Gellan gum has been reported to have wide pharmaceutical applications such as tablet binder, disintegrant, gelling agent and as a controlled release polymer. Multiparticulate delivery systems spread out more uniformly in the gastrointestinal tract and reduce the local irritation. The purpose of this study is to explore possible applicability of gellan macro beads as an oral controlled release system of a sparingly soluble drug, amoxicillin. Gellan gum beads were prepared by ionotropic gelation with calcium ions. The effect of drug loading, stirring time, polymer concentration, electrolyte (CaCl2) concentration, curing time etc. influencing the preparation of the gellan gum macro beads and the drug release from gellan gum beads were investigated in this study. Optimal preparation conditions allowed very high incorporation efficiency for amoxicillin (91%) The release kinetics of amoxicillin from gellan beads followed the diffusion model for an inert porous matrix in the order: 0.1 N HCl > phosphate buffer > distilled water. Change in curing time did not significantly affect the release rate constant, but drug concentration, polymer concentration and electrolyte concentration significantly affect the release rate of amoxicillin from the beads. The gellan macro beads may be suitable for gastro retentive controlled delivery of amoxicillin.

  8. Hybrid mesoporous silica nanocarriers with thermovalve-regulated controlled release.

    PubMed

    Ribeiro, T; Coutinho, E; Rodrigues, A S; Baleizão, C; Farinha, J P S

    2017-09-01

    Mesoporous silica nanoparticles (MSNs) are excellent nanocarriers, featuring very high cargo capacity due to their large surface area and pore volume. The particle and pore dimensions can be accurately tuned, and both the internal and external surfaces allow versatile functionalization. We developed hybrid MSNs with diameters around 140 nm, with the external surface selectively modified with a temperature-responsive biocompatible copolymer to control cargo release. The nanoparticles feature either a polymer brush or a gel-like responsive shell, produced by grafting from RAFT polymerization of PEG-acrylate macromonomers. The hybrid nanoparticles have fluorescent molecules incorporated into the inorganic network providing excellent optical properties for traceability and imaging. The cargo release profiles are explained by a temperature-controlled "pumping" mechanism: at low temperature (ca. 20 °C) the polymer shell is hydrophilic and expanded, opposing cargo diffusion out of the shell and retaining the molecules released from the mesopores; above room temperature (ca. 40-50 °C) the polymer network becomes more hydrophobic and collapses onto the silica surface, releasing the cargo by a sponge-like squeezing effect. The release kinetics depends on the polymer shell type, with better results obtained for the gel-coated nanoparticles. Our proof-of-concept system shows that by modulating the temperature, it is possible to achieve a pumping regime that increases the release rate in a controlled way.

  9. Intravaginal flux controlled pump for sustained release of macromolecules.

    PubMed

    Teller, Ryan S; Rastogi, Rachna; Johnson, Todd J; Blair, Michael J; Hitchcock, Robert W; Kiser, Patrick F

    2014-09-01

    To design a flux controlled pump (FCP) capable of 30-day, controlled release of macromolecules to the vaginal mucosa. The FCP is composed of a single chamber fabricated from a rigid thermoplastic with orifices and encloses a pellet of water-swellable polymer containing the drug substance. We performed testing both in vitro and in rabbits. To ensure vaginal retention in the rabbit, we designed and attached an oval shape-memory polyether urethane retainer to the FCP allowing for long-term intravaginal evaluation of a solid dosage form without invasive surgical implantation. The orifices and swelling properties of the polymer pellet control water entry for polymer hydration and expansion, and subsequent extrusion of the drug-containing gel from the orifice. A FCP device containing a pellet composed of hydroxypropyl cellulose compounded with a model macromolecule, achieved controlled in vitro release for 30 days with an average release rate of 24 ± 2 μg/day (mean ± SD) and range of 16 to 42 μg/day. We observed a slightly lower average release rate in vivo of 20 ± 0.6 μg/day (mean ± SD). The size of the orifice and nature of the swelling polymer controls the hydration rate and thereby macromolecule release rate and duration from this FCP.

  10. Understanding and managing the impact of HPMC variability on drug release from controlled release formulations.

    PubMed

    Zhou, Deliang; Law, Devalina; Reynolds, Judie; Davis, Lynn; Smith, Clifford; Torres, Jose L; Dave, Viraj; Gopinathan, Nishanth; Hernandez, Daniel T; Springman, Mary Kay; Zhou, Casey Chun

    2014-06-01

    The purpose of this study is to identify critical physicochemical properties of hydroxypxropyl methylcellulose (HPMC) that impact the dissolution of a controlled release tablet and develop a strategy to mitigate the HPMC lot-to-lot and vendor-to-vendor variability. A screening experiment was performed to evaluate the impacts of methoxy/hydroxypropyl substitutions, and viscosity on drug release. The chemical diversity of HPMC was explored by nuclear magnetic resonance (NMR), and the erosion rate of HPMC was investigated using various dissolution apparatuses. Statistical evaluation suggested that the hydroxypropyl content was the primary factor impacting the drug release. However, the statistical model prediction was not robust. NMR experiments suggested the existence of structural diversity of HPMC between lots and more significantly between vendors. Review of drug release from hydrophilic matrices indicated that erosion is a key aspect for both poorly soluble and soluble drugs. An erosion rate method was then developed, which enabled the establishment of a robust model and a meaningful HPMC specification. The study revealed that the overall substitution level is not the unique parameter that dictates its release-controlling properties. Fundamental principles of polymer chemistry and dissolution mechanisms are important in the development and manufacturing of hydrophilic matrices with consistent dissolution performance.

  11. Sol-gel encapsulation for controlled drug release and biosensing

    NASA Astrophysics Data System (ADS)

    Fang, Jonathan

    The main focus of this dissertation is to investigate the use of sol-gel encapsulation of biomolecules for controlled drug release and biosensing. Controlled drug release has advantages over conventional therapies in that it maintains a constant, therapeutic drug level in the body for prolonged periods of time. The anti-hypertensive drug Captopril was encapsulated in sol-gel materials of various forms, such as silica xerogels and nanoparticles. The primary objective was to show that sol-gel silica materials are promising drug carriers for controlled release by releasing Captopril at a release rate that is within a therapeutic range. We were able to demonstrate desired release for over a week from Captopril-doped silica xerogels and overall release from Captopril-doped silica nanoparticles. As an aside, the antibiotic Vancomycin was also encapsulated in these porous silica nanoparticles and desired release was obtained for several days in-vitro. The second part of the dissertation focuses on immobilizing antibodies and proteins in sol-gel to detect various analytes, such as hormones and amino acids. Sol-gel competitive immunoassays on antibody-doped silica xerogels were used for hormone detection. Calibration for insulin and C-peptide in standard solutions was obtained in the nM range. In addition, NASA-Ames is also interested in developing a reagentless biosensor using bacterial periplasmic binding proteins (bPBPs) to detect specific biomarkers, such as amino acids and phosphate. These bPBPs were doubly labeled with two different fluorophores and encapsulated in silica xerogels. Ligand-binding experiments were performed on the bPBPs in solution and in sol-gel. Ligand-binding was monitored by fluorescence resonance energy transfer (FRET) between the two fluorophores on the bPBP. Titration data show that one bPBP has retained its ligand-binding properties in sol-gel.

  12. Oral controlled-release formulation in veterinary medicine.

    PubMed

    Lavy, Eran; Steinman, Amir; Soback, Stefan

    2006-01-01

    The development of controlled-release dosage forms (CRDFs) is highly desirable both from a convenience and compliance perspective. Furthermore, these formulations release drugs at a prescribed rate, leading to relatively constant blood drug concentrations or to pulse dosing. Another benefit is the ability to administer medications in infrequent regimens. For example, antimicrobial agents generally require very frequent administration regimens. In recent years, the pharmaceutical industry has realized the potential of this treatment modality and efforts have been made to develop a variety of CRDFs exclusively for veterinary use. While there are a number of controlled-release products available for veterinary applications, only a limited number of therapeutic niches (such as the application of antiparasitic drugs in cattle) are associated with products that have been developed as oral controlled-release products. In addition to reviewing potential new therapeutic areas where oral controlled-release products can be applied in veterinary medicine, this article reviews differences in the gastrointestinal tracts of various species and the significance of the dissimilarity in the development of CRDFs. Technological aspects involved in veterinary CRDFs are also assessed.

  13. Wetting mechanisms of gel-based controlled-release fertilizers.

    PubMed

    Shavit, U; Reiss, M; Shaviv, A

    2003-02-14

    The release mechanism of gel-based controlled release fertilizers (CRFs) involves water penetration into dry mixtures of fertilizers and gel forming polymers. Water penetration provides an upper limit to the whole release process. Where wetting prediction is often based on models that describe the flow of the liquid phase, vapor motion may become significant when a sharp wetting front exists. In this study we examine the role of vapor and fluid flows in the wetting process of CRFs consisting of urea or KNO(3) mixed with polyacrylamide (PAM). Vapor adsorption isotherms were obtained for typical fertilizer-PAM mixtures. Wetting and release experiments were conducted by dividing the CRFs into regions alternately filled with a pure fertilizer and mixtures of PAM and fertilizer. The experiments were designed in such a way that when the wetting front reaches a mixtures interface, its motion depends on the gradient imposed by the difference in osmotic potential (OP). The coupled equations of vapor and liquid flow in initially dry conditions were solved numerically to demonstrate the conceptual understanding gained by the experiments. The results show that wetting front motion is affected by transport and adsorption of vapor. It was also shown that the release rate is different when wetting is governed by vapor flow or by liquid flow. The release pattern from a multi-regions device was consistent with the wetting pattern, demonstrating the possibility to tailor the release according to periods of peak demand.

  14. Fusion pores and their control of neurotransmitter and hormone release

    PubMed Central

    Chang, Che-Wei; Chiang, Chung-Wei

    2017-01-01

    Ca2+-triggered exocytosis functions broadly in the secretion of chemical signals, enabling neurons to release neurotransmitters and endocrine cells to release hormones. The biological demands on this process can vary enormously. Although synapses often release neurotransmitter in a small fraction of a millisecond, hormone release can be orders of magnitude slower. Vesicles usually contain multiple signaling molecules that can be released selectively and conditionally. Cells are able to control the speed, concentration profile, and content selectivity of release by tuning and tailoring exocytosis to meet different biological demands. Much of this regulation depends on the fusion pore—the aqueous pathway by which molecules leave a vesicle and move out into the surrounding extracellular space. Studies of fusion pores have illuminated how cells regulate secretion. Furthermore, the formation and growth of fusion pores serve as a readout for the progress of exocytosis, thus revealing key kinetic stages that provide clues about the underlying mechanisms. Herein, we review the structure, composition, and dynamics of fusion pores and discuss the implications for molecular mechanisms as well as for the cellular regulation of neurotransmitter and hormone release. PMID:28167663

  15. Controlled-release nanoencapsulating microcapsules to combat inflammatory diseases

    PubMed Central

    Baek, Jong-Suep; Yeo, Eng Wan; Lee, Yin Hao; Tan, Nguan Soon; Loo, Say Chye Joachim

    2017-01-01

    The World Health Organization (WHO) has reported that globally 235 million people suffer from chronic and other inflammatory diseases. The short half-lives of nonsteroidal anti-inflammatory drugs (NSAIDs) and their notoriety in causing gastrointestinal discomforts, warrants these drugs to be released in a controlled and sustained manner. Although polymeric particles have been widely used for drug delivery, there are few reports that showcase their ability in encapsulating and sustaining the release of NSAIDs. In this paper, polymeric nanoencapsulating microcapsules loaded with NSAIDs were fabricated using solid/water/oil/water emulsion solvent evaporation method. Two NSAIDs, ibuprofen and naproxen, were first pre-loaded into nanoparticles and then encapsulated into a larger hollow microcapsule that contained the third NSAID, celecoxib. A high encapsulation efficiency (%) of these NSAIDs was achieved and a sustained release (up to 30 days) of these drugs in phosphate-buffered saline was observed. Then, a gastrointestinal drug – cimetidine (CIM) – was co-loaded with the NSAIDs. This floating delivery system exhibited excellent buoyancy (~88% up to 24 h) in simulated gastric fluid. It also allowed a sequential release of the drugs, whereby an immediate release of CIM followed by NSAIDs was observed. Drug release of the NSAIDs observed Fickian diffusion mechanism, whereas CIM observed non-Fickian diffusion. Therefore, this delivery system is a promising platform to control the delivery of NSAIDs to combat inflammatory diseases, thereby protecting against possible gastrointestinal side effects that may arise from the overuse of NSAIDs. PMID:28652708

  16. Tolbutamide Controls Glucagon Release From Mouse Islets Differently Than Glucose

    PubMed Central

    Cheng-Xue, Rui; Gómez-Ruiz, Ana; Antoine, Nancy; Noël, Laura A.; Chae, Hee-Young; Ravier, Magalie A.; Chimienti, Fabrice; Schuit, Frans C.; Gilon, Patrick

    2013-01-01

    We evaluated the role of ATP-sensitive K+ (KATP) channels, somatostatin, and Zn2+ in the control of glucagon secretion from mouse islets. Switching from 1 to 7 mmol/L glucose inhibited glucagon release. Diazoxide did not reverse the glucagonostatic effect of glucose. Tolbutamide decreased glucagon secretion at 1 mmol/L glucose (G1) but stimulated it at 7 mmol/L glucose (G7). The reduced glucagon secretion produced by high concentrations of tolbutamide or diazoxide, or disruption of KATP channels (Sur1−/− mice) at G1 could be inhibited further by G7. Removal of the somatostatin paracrine influence (Sst−/− mice or pretreatement with pertussis toxin) strongly increased glucagon release, did not prevent the glucagonostatic effect of G7, and unmasked a marked glucagonotropic effect of tolbutamide. Glucose inhibited glucagon release in the absence of functional KATP channels and somatostatin signaling. Knockout of the Zn2+ transporter ZnT8 (ZnT8−/− mice) did not prevent the glucagonostatic effect of glucose. In conclusion, glucose can inhibit glucagon release independently of Zn2+, KATP channels, and somatostatin. Closure of KATP channels controls glucagon secretion by two mechanisms, a direct stimulation of α-cells and an indirect inhibition via somatostatin released from δ-cells. The net effect on glucagon release results from a balance between both effects. PMID:23382449

  17. Controlled Release of Chlorhexidine from UDMA-TEGDMA Resin

    PubMed Central

    Anusavice, K.J.; Zhang, N.-Z.; Shen, C.

    2008-01-01

    Chlorhexidine salts are available in various formulations for dental applications. This study tested the hypothesis that the release of chlorhexidine from a urethane dimethacrylate and triethylene glycol dimethacrylate resin system can be effectively controlled by the chlorhexidine diacetate content and pH. The filler concentrations were 9.1, 23.1, or 33.3 wt%, and the filled resins were exposed to pH 4 and pH 6 acetate buffers. The results showed that Fickian diffusion was the dominant release mechanism. The rates of release were significantly higher in pH 4 buffer, which was attributed to the increase of chlorhexidine diacetate solubility at lower pH. The higher level of filler loading reduced the degree of polymerization, leading to a greater loss of organic components and higher chlorhexidine release rates. PMID:16998139

  18. Controlled release of chlorhexidine from UDMA-TEGDMA resin.

    PubMed

    Anusavice, K J; Zhang, N-Z; Shen, C

    2006-10-01

    Chlorhexidine salts are available in various formulations for dental applications. This study tested the hypothesis that the release of chlorhexidine from a urethane dimethacrylate and triethylene glycol dimethacrylate resin system can be effectively controlled by the chlorhexidine diacetate content and pH. The filler concentrations were 9.1, 23.1, or 33.3 wt%, and the filled resins were exposed to pH 4 and pH 6 acetate buffers. The results showed that Fickian diffusion was the dominant release mechanism. The rates of release were significantly higher in pH 4 buffer, which was attributed to the increase of chlorhexidine diacetate solubility at lower pH. The higher level of filler loading reduced the degree of polymerization, leading to a greater loss of organic components and higher chlorhexidine release rates.

  19. Application of cellulose acetate for controlled release of thymol.

    PubMed

    Milovanovic, Stoja; Markovic, Darka; Aksentijevic, Ksenija; Stojanovic, Dusica B; Ivanovic, Jasna; Zizovic, Irena

    2016-08-20

    Cellulose acetate (CA) was investigated as a carrier towards development of material with controlled release of thymol as a natural substance with strong antibacterial properties using high pressure techniques. Effect of thymol content on CA was confirmed by SEM, FTIR and DSC methods. Kinetic of thymol release from CA was tested using simulated gastric and intestinal fluids (hydrochloric acid and phosphate buffer saline). Results were correlated with Korsmeyer-Peppas and Weibull model. Depending on the thymol content and chemical nature of the release medium, the time of thymol release varied from one to three days indicating CA as a promising carrier of thymol with potential uses from medicine to agriculture. The impregnated CA showed antibacterial activity against 23 tested bacterial strains including methicillin-resistant Staphylococcus aureus (MRSA) which is particularly important bearing in mind that this strain causes fatal infections in humans and animals.

  20. Method and apparatus for controlling accidental releases of tritium

    DOEpatents

    Galloway, Terry R. [Berkeley, CA

    1980-04-01

    An improvement in a tritium control system based on a catalytic oxidation reactor wherein accidental releases of tritium into room air are controlled by flooding the catalytic oxidation reactor with hydrogen when the tritium concentration in the room air exceeds a specified limit. The sudden flooding with hydrogen heats the catalyst to a high temperature within seconds, thereby greatly increasing the catalytic oxidation rate of tritium to tritiated water vapor. Thus, the catalyst is heated only when needed. In addition to the heating effect, the hydrogen flow also swamps the tritium and further reduces the tritium release.

  1. Method and apparatus for controlling accidental releases of tritium

    DOEpatents

    Galloway, T.R.

    1980-04-01

    An improvement is described in a tritium control system based on a catalytic oxidation reactor wherein accidental releases of tritium into room air are controlled by flooding the catalytic oxidation reactor with hydrogen when the tritium concentration in the room air exceeds a specified limit. The sudden flooding with hydrogen heats the catalyst to a high temperature within seconds, thereby greatly increasing the catalytic oxidation rate of tritium to tritiated water vapor. Thus, the catalyst is heated only when needed. In addition to the heating effect, the hydrogen flow also swamps the tritium and further reduces the tritium release. 1 fig.

  2. Press-coating of immediate release powders onto coated controlled release tablets with adhesives.

    PubMed

    Waterman, Kenneth C; Fergione, Michael B

    2003-05-20

    A novel adhesive coating was developed that allows even small quantities of immediate-release (IR) powders to be press-coated onto controlled-release (CR), coated dosage forms without damaging the CR coating. The process was exemplified using a pseudoephedrine osmotic tablet (asymmetric membrane technology, AMT) where a powder weighing less than 25% of the core was pressed onto the osmotic tablet providing a final combination tablet with low friability. The dosage form with the adhesive plus the press-coated powder showed comparable sustained drug release rates to the untreated dosage form after an initial 2-h lag. The adhesive layer consisted of an approximately 100- microm coating of Eudragit RL, polyethylene glycol (PEG) and triethyl citrate (TEC) at a ratio of 5:3:1.2. This coating provides a practical balance between handleability before press-coating and good adhesion.

  3. Hydroxyapatite particles as a controlled release carrier of protein.

    PubMed

    Matsumoto, T; Okazaki, M; Inoue, M; Yamaguchi, S; Kusunose, T; Toyonaga, T; Hamada, Y; Takahashi, J

    2004-08-01

    This study examines the possibility of using hydroxyapatite (HAp) particles as a controlled release carrier of protein. In order to achieve effective protein release from HAp particles, it is necessary to regulate the conjugated amount of protein on HAp and the resorption of HAp. HAp particles were synthesized at different temperatures (40 degrees C, 60 degrees C, 80 degrees C) in wet condition and the physico-chemical properties of synthesized HAp particles were examined. HAp particles synthesized at low temperatures showed low crystallinity, high solubility and large specific surface area. The useful growth factors for bone regeneration, such as BMP, bFGF and TGF-beta, are basic proteins, so cytochrome c (pI=10.2) was used as a model protein and the adsorptive property of protein on HAp particles was investigated. The protein adsorption on HAp particles changed depending on its specific surface area and the chart of protein adsorption on HAp particles showed a typical Langmuir curve. These findings suggest that the adsorbed amount of protein on HAp particles could be regulated by HAp synthesizing temperature and the concentrations of protein solution. The release kinetics of protein from the HAp particles that adsorbed the protein (HAp-pro) was also evaluated in different pH solutions (pH 4.0 and 7.0). The released protein gradually increased time dependently when HAp-pro were immersed in pH 4.0 solution, but the released protein was significantly smaller when HAp-pro were immersed in pH 7.0 solution. Moreover, the release rate of protein from HAp-pro differed in each HAp that was synthesized at different temperatures, suggesting that the release of protein from HAp-pro depended on HAp resorption. These results suggest that HAp particles synthesized at different temperature are useful as a controlled release carrier of protein.

  4. Controlled Release of Multiple Therapeutics from Silicone Hydrogel Contact Lenses

    PubMed Central

    White, Charles J.; DiPasquale, Stephen A.; Byrne, Mark E.

    2016-01-01

    Purpose The majority of contact lens wearers experience a significant level of ocular discomfort associated with lens wear, often within hours of wear, related to dry lenses, inflammation, protein adhesion to the lens surface, etc. Application of controlled drug release techniques has focused on the incorporation and/or release of a single comfort molecule from a lens including high molecular weight comfort agents or pharmaceutical agents. Previous studies have sought to mitigate the occurrence of only single propagators of discomfort. Clinical studies with eye drop solutions have shown that a mixture of diverse comfort agents selected to address multiple propagators of discomfort provide the greatest and longest lasting sensations of comfort for the patient. In this paper, multiple propagators of discomfort are addressed through the simultaneous release of four molecules from a novel contact lens to ensure high level of lens wear comfort. Methods Silicone hydrogel contact lenses were engineered via molecular imprinting strategies to simultaneously release up to four template molecules including hydropropyl methylcellulose (HPMC), trehalose, ibuprofen, and prednisolone. Results By adjusting the ratio of functional monomer to comfort molecule, a high level of control was demonstrated over the release rate. HPMC, trehalose, ibuprofen, and prednisolone were released at therapeutically relevant concentrations with varying rates from a single lens. Conclusions The results indicate use as daily disposable lenses for single day release or extended-wear lenses with multiple day release. Imprinted lenses are expected to lead to higher efficacy for patients compared to topical eye drops by improving compliance and mitigating concentration peaks and valleys associated with multiple drops. PMID:26945177

  5. Controlled release matrix tablets of olanzapine: influence of polymers on the in vitro release and bioavailability.

    PubMed

    Badshah, Amir; Subhan, Fazal; Rauf, Khalid

    2010-09-01

    Controlled-release (CR) tablet formulation of olanzapine was developed using a binary mixture of Methocel® K100 LV-CR and Ethocel® standard 7FP premium by the dry granulation slugging method. Drug release kinetics of CR tablet formulations F1, F2, and F3, each one suitably compressed for 9-, 12-, and 15-kg hardness, were determined in a dissolution media of 0.1 N HCl (pH 1.5) and phosphate buffer (pH 6.8) using type II dissolution apparatus with paddles run at 50 rpm. Ethocel® was found to be distinctly controlling drug release, whereas the hardness of tablets and pH of the dissolution media did not significantly affect release kinetics. The CR test tablets containing 30% Methocel® and 60% Ethocel® (F3) with 12-kg hardness exhibited pH-independent zero-order release kinetics for 24 h. In vivo performance of the CR test tablet and conventional reference tablet were determined in rabbit serum using high-performance liquid chromatography coupled with electrochemical detector. Bioavailability parameters including C(max), T(max), and AUC(0-48 h) of both tablets were compared. The CR test tablets produced optimized C(max) and extended T(max) (P < 0.05). A good correlation of drug absorption in vivo and drug release in vitro (R(2) = 0.9082) was observed. Relative bioavailability of the test tablet was calculated as 94%. The manufacturing process employed was reproducible and the CR test tablets were stable for 6 months at 40 ± 2°C/75 ± 5% relative humidity. It was concluded that the CR test tablet formulation successfully developed may improve tolerability and patient adherence by reducing adverse effects.

  6. Motor control differs for increasing and releasing force

    PubMed Central

    Park, Seoung Hoon; Kwon, MinHyuk; Solis, Danielle; Lodha, Neha

    2016-01-01

    Control of the motor output depends on our ability to precisely increase and release force. However, the influence of aging on force increase and release remains unknown. The purpose of this study, therefore, was to determine whether force control differs while increasing and releasing force in young and older adults. Sixteen young adults (22.5 ± 4 yr, 8 females) and 16 older adults (75.7 ± 6.4 yr, 8 females) increased and released force at a constant rate (10% maximum voluntary contraction force/s) during an ankle dorsiflexion isometric task. We recorded the force output and multiple motor unit activity from the tibialis anterior (TA) muscle and quantified the following outcomes: 1) variability of force using the SD of force; 2) mean discharge rate and variability of discharge rate of multiple motor units; and 3) power spectrum of the multiple motor units from 0–4, 4–10, 10–35, and 35–60 Hz. Participants exhibited greater force variability while releasing force, independent of age (P < 0.001). Increased force variability during force release was associated with decreased modulation of multiple motor units from 35 to 60 Hz (R2 = 0.38). Modulation of multiple motor units from 35 to 60 Hz was further correlated to the change in mean discharge rate of multiple motor units (r = 0.66) and modulation from 0 to 4 Hz (r = −0.64). In conclusion, these findings suggest that force control is altered while releasing due to an altered modulation of the motor units. PMID:26961104

  7. Do CYP2D6 genotypes reflect oxycodone requirements for cancer patients treated for cancer pain? A cross-sectional multicentre study.

    PubMed

    Andreassen, Trine Naalsund; Eftedal, Ingrid; Klepstad, Pål; Davies, Andrew; Bjordal, Kristin; Lundström, Staffan; Kaasa, Stein; Dale, Ola

    2012-01-01

    Opioids are recommended by the World Health Organization for moderate to severe cancer pain. Oxycodone is one of the most commonly used opioids and is metabolized in the liver by CYP3A4 and CYP2D6 enzymes. The aim of this cross-sectional study was to assess the relationship between oxycodone pharmacokinetics, pharmacodynamics and the CYP2D6 genotypes "poor metaboliser" (PM), "extensive metaboliser" (EM) and "ultra-rapid metaboliser" (URM) in a cohort of patients with cancer pain. The patients were genotyped for the most common CYP2D6 variants and serum concentrations of oxycodone and metabolites were determined. Pain was assessed using the Brief Pain Inventory (BPI). The EORTC QLQ-C30 was used to assess the symptoms of tiredness and nausea. Cognitive function was assessed by the Mini Mental State (MMS) examination. Associations were examined by analyses of variance (ANOVA) and covariance (ANCOVA), or ordinal logistic regressions with and without covariates. The sample consisted of 27 PM, 413 EM (including heterozygotes) and 10 URM. PM had lower oxymorphone and noroxymorphone serum concentrations and oxymorphone to oxycodone ratios than EM and URM. No differences between PM, EM and URM in pain intensity, nausea, tiredness or cognitive function was found. CYP2D6 genotypes caused expected differences in pharmacokinetics, but they had no pharmacodynamic consequence. CYP2D6 genotypes did not influence pain control, the adverse symptoms nausea and sedation or the risk for cognitive failure in this study of patients treated with oxycodone for cancer pain.

  8. Controlled release tablet formulation containing natural Δ(9)-tetrahydrocannabinol.

    PubMed

    Punyamurthula, Nagendra S; Hingorani, Tushar; Adelli, Goutham; Gul, Waseem; ElSohly, Mahmoud A; Repka, Michael A; Majumdar, Soumyajit

    2016-01-01

    Cannabinoids are increasingly being used in the treatment of chemotherapy-induced nausea and vomiting (CINV) because of their action on the cannabinoid receptors, CB1 and CB2. The currently marketed capsule formulations (sesame oil based and crystalline powder) are required to be administered frequently to maintain therapeutic levels, which leads to non-compliance. In the present study, oral controlled release tablet formulations of Δ(9)-tetrahydrocannabinol (THC) were prepared using the lipids Precirol® and Compritol®. Release profiles using THC-lipid matrices and/or with the lipids in the external phase (blend) were evaluated. The effect of directly compressible diluents lactose mixture (Ludipress®), dicalcium phosphate anhydrous (Emcompress®) and microcrystalline cellulose (Avicel® 102) on tablet characteristics and in vitro drug release was also investigated. Further, in vitro THC release in the presence of a lipase inhibitor, Pluronic® F68, was also studied. A 24 h zero-order THC release profile was obtained with a combination of Precirol® and Compritol® in the compression blend. Addition of Pluronic® F68 did not alter THC release in vitro. These optimized tablets were chemically and physically stable for 3 months, the last time point tested, at 25 °C/60% RH. The overall results demonstrate the feasibility of preparing oral THC tablets for once a day administration which can improve CINV management.

  9. Mechanisms controlling theophylline release from ethanol-resistant coated pellets.

    PubMed

    Rosiaux, Y; Velghe, C; Muschert, S; Chokshi, R; Leclercq, B; Siepmann, F; Siepmann, J

    2014-03-01

    To elucidate the mass transport mechanisms controlling drug release from recently proposed, ethanol-resistant, polymeric film coatings. Theophylline matrix pellets were coated with ethylcellulose: guar gum blends. Drug release from single pellets and ensembles of pellets was measured in various release media. Changes in the systems' morphology, composition and mechanical properties were monitored using SEM, gravimetrical analysis and a texture analyzer. Based on the obtained experimental results a mechanistically realistic mathematical model was identified and used to quantitatively predict drug release from coated pellets in ethanol-free and ethanol-containing bulk fluids. Drug diffusion though the intact polymeric film coatings is likely to be the dominant mass transport mechanism in the investigated systems, irrespective of the ethanol content in the surrounding environment. An appropriate solution of Fick's law could be used to quantitatively predict theophylline release from pellets coated with different ethylcellulose:guar gum blends at different coating levels. Importantly, independent experiments confirmed the theoretical predictions. In silico simulations can help facilitating the optimization of the novel ethanol-resistant polymeric film coatings, avoiding time-consuming and cost-intensive series of trial-and-error experiments. The presence/absence of ethanol does not affect the underlying drug release mechanisms.

  10. Controlled release of alendronate from nitrogen-doped mesoporous carbon

    DOE PAGES

    Saha, Dipendu; Spurri, Amanda; Chen, Jihua; ...

    2016-04-13

    With this study, we have synthesized a nitrogen doped mesoporous carbon with the BET surface area of 1066 m2/g, total pore volume 0.6 cm3/g and nitrogen content of 0.5%. Total alendronate adsorption in this carbon was ~5%. The release experiments were designed in four different media with sequential pH values of 1.2, 4.5, 6.8 and 7.4 for 3, 1, 3 and 5 h, respectively and at 37 °C to imitate the physiological conditions of stomach, duodenum, small intestine and colon, respectively. Release of the drug demonstrated a controlled fashion; only 20% of the drug was released in the media withmore » pH = 1.2, whereas 64% of the drug was released in pH = 7.4. This is in contrary to pure alendronate that was completely dissolved within 30 min in the first release media (pH = 1.2) only. The relatively larger uptake of alendronate in this carbon and its sustained fashion of release can be attributed to the hydrogen bonding between the drug and the nitrogen functionalities on carbon surface. Based on this result, it can be inferred that this formulation may lower the side effects of oral delivery of alendronate.« less

  11. Controlled release of alendronate from nitrogen-doped mesoporous carbon

    SciTech Connect

    Saha, Dipendu; Spurri, Amanda; Chen, Jihua; Hensley, Dale K.

    2016-04-13

    With this study, we have synthesized a nitrogen doped mesoporous carbon with the BET surface area of 1066 m2/g, total pore volume 0.6 cm3/g and nitrogen content of 0.5%. Total alendronate adsorption in this carbon was ~5%. The release experiments were designed in four different media with sequential pH values of 1.2, 4.5, 6.8 and 7.4 for 3, 1, 3 and 5 h, respectively and at 37 °C to imitate the physiological conditions of stomach, duodenum, small intestine and colon, respectively. Release of the drug demonstrated a controlled fashion; only 20% of the drug was released in the media with pH = 1.2, whereas 64% of the drug was released in pH = 7.4. This is in contrary to pure alendronate that was completely dissolved within 30 min in the first release media (pH = 1.2) only. The relatively larger uptake of alendronate in this carbon and its sustained fashion of release can be attributed to the hydrogen bonding between the drug and the nitrogen functionalities on carbon surface. Based on this result, it can be inferred that this formulation may lower the side effects of oral delivery of alendronate.

  12. Oxycodone-induced conditioned place preference and sensitization of locomotor activity in adolescent and adult mice

    PubMed Central

    Niikura, Keiichi; Ho, Ann; Kreek, Mary Jeanne; Zhang, Yong

    2013-01-01

    Nonmedical use of the prescription opioid oxycodone has become a major public health problem in the United States, with special concern for adolescents. Although adults and adolescents have different sensitivities for drugs, little is known about the rewarding effects of oxycodone in adolescents compared to adults, even in rodent models. Here, we investigate sensitivity to oxycodone by the conditioned place preference assay of conditioned reward, and effect on the locomotor activity in adolescent (4 weeks old) and adult (10 weeks old) C57BL/6J mice. Mice of both ages were trained with multiple doses of oxycodone (0, 0.3, 1, and 3 mg/kg) and showed conditioned preference in a dose-dependent manner. The adult mice developed conditioned preference to the lowest dose tested (0.3 mg/kg), but adolescent mice did not. Dose-dependent oxycodone-induced increases in locomotor activity were observed across the conditioning session. Interestingly, adolescent mice developed greater sensitization to the locomotor-activating effects of oxycodone than adult mice. Thus differences in sensitivity to oxycodone, such as the lower initial sensitivity for conditioned preference but greater locomotor sensitization in adolescent mice, may indicate contributing factors in oxycodone abuse and later addiction in human adolescents. PMID:23827650

  13. CYP2D6 pharmacogenetic and oxycodone pharmacokinetic association study in pediatric surgical patients.

    PubMed

    Balyan, Rajiv; Mecoli, Marc; Venkatasubramanian, Raja; Chidambaran, Vidya; Kamos, Nichole; Clay, Smokey; Moore, David L; Mavi, Jagroop; Glover, Chris D; Szmuk, Peter; Vinks, Alexander; Sadhasivam, Senthilkumar

    2017-03-01

    Oxycodone is partly metabolized to the active metabolite oxymorphone by hepatic CYP2D6 in the liver. Significant genetic variability in CYP2D6 activity affects oxymorphone formation. This study aimed to associate CYP2D6 genotype and oxycodone's metabolism. 30 children were administered oral oxycodone postoperatively. Plasma levels of oxycodone and oxymorphone, and CYP2D6 genotype were analyzed. CYP2D6 genotype and oxycodone metabolism phenotype were determined based on CYP2D6 total activity score (TAS) and metabolism phenotype: poor metabolizer (PM), intermediate metabolizer (IM), extensive metabolizer (EM) or ultrarapid metabolizer (UM). Compared with PM/IM subjects, significantly greater oxymorphone exposure was seen in EM subjects (p = 0.02 for Cmax, p = 0.016 for AUC0-6 and p = 0.026 for AUC0-24). Similarly, higher TAS value was found to be associated with greater oxymorphone exposure. Higher conversion of oxycodone to oxymorphone was observed in EM subjects compared with PM/IM subjects (p = 0.0007 for Cmax, p = 0.001 for AUC0-6 and p = 0.004 for AUC0-24). CYP2D6 phenotypes explain metabolism of oxycodone in children, and oxymorphone exposure is higher in CYP2D6 EM phenotype. Further studies are needed to predict the occurrence of adverse event and tailor oxycodone dose for a specific CYP2D6 phenotype.

  14. Pharmacokinetics of oxycodone after intravenous and subcutaneous administration in Japanese patients with cancer pain.

    PubMed

    Kokubun, Hideya; Yoshimoto, Tetsusuke; Hojo, Minoru; Fukumura, Kazuya; Matoba, Motohiro

    2014-12-01

    ABSTRACT In Japan, Oxycodone hydrochloride injection formulation has been approved in 2012. However, its pharmacokinetics has been poorly studied. The aim of this study is to evaluate the pharmacokinetics of oxycodone after intravenous and subcutaneous administration of oxycodone hydrochloride injection in Japanese patients with cancer pain. Noncompartmental analysis and population pharmacokinetic analysis were performed. We conducted a multicenter open-label study of oxycodone hydrochloride administered as constant infusion with the dose titrated individually according to the pain intensity in patients with cancer pain. Pharmacokinetic parameters for plasma oxycodone and its metabolites were estimated using pharmacokinetics of oxycodone was evaluated using a total of 344 plasma concentrations obtained from 89 patients. The estimated geometric mean clearance (CL) of oxycodone was 24.3 L per hour after constant intravenous infusion and 29.5 L per hour after constant subcutaneous infusion, respectively. Population pharmacokinetic analysis indicated that body surface area was the influencing factor on CL and there were no pharmacokinetic differences for CL between intravenous and subcutaneous infusion. These results provide important information for the clinical use of oxycodone injection.

  15. Receptors controlling transmitter release from sympathetic neurons in vitro.

    PubMed

    Boehm, S; Huck, S

    1997-02-01

    Primary cultures of postganglionic sympathetic neurons were established more than 30 years ago. More recently, these cultures have been used to characterize various neurotransmitter receptors that govern sympathetic transmitter release. These receptors may be categorized into at least three groups: (1) receptors which evoke transmitter release: (2) receptors which facilitate; (3) receptors which inhibit, depolarization-evoked release. Group (1) comprises nicotinic and muscarinic acetylcholine receptors, P2X purinoceptors and pyrimidinoceptors. Group (2) currently harbours beta-adrenoceptors, P2 purinoceptors, receptors for PACAP and VIP, as well as prostanoid EP1 receptors. In group (3), muscarinic cholinoceptors, alpha 2- and beta-adrenoceptors, P2 purinoceptors, and receptors for the neuropeptides NPY, somatostatin (SRIF1) and LHRH, as well as opioid (delta and kappa) receptors can be found. Receptors which regulate transmitter release from neurons in cell culture may be located either at the somatodendritic region or at the sites of exocytosis, i.e. the presynaptic specializations of axons. Most of the receptors that evoke release are located at the soma. There ionotropic receptors cause depolarizations to generate action potentials which then trigger Ca(2+)-dependent exocytosis at axon terminals. The signalling mechanisms of metabotropic receptors which evoke release still remain to be identified. Receptors which facilitate depolarization-evoked release appear to be located preferentially at presynaptic sites and presumably act via an increase in cyclic AMP. Receptors which inhibit stimulation evoked release are also presynaptic origin and most commonly rely on a G protein-mediated blockade of voltage-gated Ca2+ channels. Results obtained with primary cell cultures of postganglionic sympathetic neurons have now supplemented previous data about neurotransmitter receptors involved in the regulation of ganglionic as well as sympatho-effector transmission. In the

  16. Controlled release of drugs from multi-component biomaterials.

    PubMed

    Zalfen, A M; Nizet, D; Jérôme, C; Jérôme, R; Frankenne, F; Foidart, J M; Maquet, V; Lecomte, F; Hubert, P; Evrard, B

    2008-11-01

    In order to control their release, drugs are encapsulated into systems which are expected to provide a certain site with a predetermined amount of drug over a well-defined period of time. Here we report on a multi-component drug delivery biomaterial that consists of a hydrogel matrix in which drug-loaded biodegradable microcarriers are dispersed, and whose potential applications could be found in the design of implantable devices with long-term activity, as required by contraceptive and hormone replacement treatments. The release profile of the drug can actually be tuned by the complex interplay of several release mechanisms, including the permeability and eventually the degradation rate of the microcarriers and the diffusion through the hydrogel. The hydrogel consisted of 2-hydroxyethyl methacrylate cross-linked by ethylene glycol dimethacrylate. The microcarriers were biodegradable poly-epsilon-caprolactone (PCL) microspheres in which active molecules, such as levonorgestrel (LNG), were encapsulated. The hydrogels were characterized by water swelling, thermal properties, LNG diffusion through drug-free and drug-depleted hydrogel membranes and LNG release from devices with drug dispersed in the hydrogel. The PCL microspheres were observed by scanning electron microscopy; their size distribution, LNG loading and release were also investigated. The hydrogel-microsphere assemblies were characterized in terms of the distribution of the microspheres within the hydrogel, water swelling and the release of the encapsulated molecules. The developed device, due to its composite structure, has the ability to combine several release mechanisms, leading to drug release obeying zero-order kinetics for most of the time.

  17. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  18. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  19. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  20. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  1. 28 CFR 541.68 - Release from controlled housing status.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Release from controlled housing status. 541.68 Section 541.68 Judicial Administration BUREAU OF PRISONS, DEPARTMENT OF JUSTICE INSTITUTIONAL MANAGEMENT INMATE DISCIPLINE AND SPECIAL HOUSING UNITS Procedures for Handling of HIV Positive Inmates...

  2. Using Randomized Controlled Trials to Evaluate Interventions for Releasing Prisoners

    ERIC Educational Resources Information Center

    Pettus-Davis, Carrie; Howard, Matthew Owen; Dunnigan, Allison; Scheyett, Anna M.; Roberts-Lewis, Amelia

    2016-01-01

    Randomized controlled trials (RCTs) are rarely used to evaluate social and behavioral interventions designed for releasing prisoners. Objective: We use a pilot RCT of a social support intervention (Support Matters) as a case example to discuss obstacles and strategies for conducting RCT intervention evaluations that span prison and community…

  3. Biopolymers in controlled release devices for agricultural applications.

    USDA-ARS?s Scientific Manuscript database

    The use of biopolymers such as starch for agricultural applications including controlled release devices is growing due the environmental benefits. Recently, concerns have grown about the worldwide spread of parasitic mites (Varroa destructor) that infect colonies of honey bees (Apis mellifera L.). ...

  4. CONTROLLED RELEASE, BLIND TEST OF DNAPL REMEDIATION BY ETHANOL FLUSHING

    EPA Science Inventory

    A dense nonaqueous phase liquid (DNAPL) source zone was established within a sheet-pile
    isolated cell through a controlled release of perchloroethylene (PCE) to evaluate DNAPL
    remediation by in-situ cosolvent flushing. Ethanol was used as the cosolvent, and the main remedia...

  5. Controlled antiseptic release by alginate polymer films and beads.

    PubMed

    Liakos, Ioannis; Rizzello, Loris; Bayer, Ilker S; Pompa, Pier Paolo; Cingolani, Roberto; Athanassiou, Athanassia

    2013-01-30

    Biodegradable polymeric materials based on blending aqueous dispersions of natural polymer sodium alginate (NaAlg) and povidone iodine (PVPI) complex, which allow controlled antiseptic release, are presented. The developed materials are either free standing NaAlg films or Ca(2+)-cross-linked alginate beads, which properly combined with PVPI demonstrate antibacterial and antifungal activity, suitable for therapeutic applications, such as wound dressing. Glycerol was used as the plasticizing agent. Film morphology was studied by optical and atomic force microscopy. It was found that PVPI complex forms well dispersed circular micro-domains within the NaAlg matrix. The beads were fabricated by drop-wise immersion of NaAlg/PVPI/glycerol solutions into aqueous calcium chloride solutions to form calcium alginate beads encapsulating PVPI solution (CaAlg/PVPI). Controlled release of PVPI was possible when the composite films and beads were brought into direct contact with water or with moist media. Bactericidal and fungicidal properties of the materials were tested against Escherichia coli bacteria and Candida albicans fungi. The results indicated very efficient antibacterial and antifungal activity within 48 h. Controlled release of PVPI into open wounds is highly desired in clinical applications to avoid toxic doses of iodine absorption by the wound. A wide variety of applications are envisioned such as external and internal wound dressings with controlled antiseptic release, hygienic and protective packaging films for medical devices, and polymer beads as water disinfectants.

  6. Using Randomized Controlled Trials to Evaluate Interventions for Releasing Prisoners

    ERIC Educational Resources Information Center

    Pettus-Davis, Carrie; Howard, Matthew Owen; Dunnigan, Allison; Scheyett, Anna M.; Roberts-Lewis, Amelia

    2016-01-01

    Randomized controlled trials (RCTs) are rarely used to evaluate social and behavioral interventions designed for releasing prisoners. Objective: We use a pilot RCT of a social support intervention (Support Matters) as a case example to discuss obstacles and strategies for conducting RCT intervention evaluations that span prison and community…

  7. CONTROLLED RELEASE, BLIND TEST OF DNAPL REMEDIATION BY ETHANOL FLUSHING

    EPA Science Inventory

    A dense nonaqueous phase liquid (DNAPL) source zone was established within a sheet-pile
    isolated cell through a controlled release of perchloroethylene (PCE) to evaluate DNAPL
    remediation by in-situ cosolvent flushing. Ethanol was used as the cosolvent, and the main remedia...

  8. Evaluation of Sterculia foetida gum as controlled release excipient.

    PubMed

    Chivate, Amit Ashok; Poddar, Sushilkumar Sharatchandra; Abdul, Shajahan; Savant, Gaurav

    2008-01-01

    The purpose of the research was to evaluate Sterculia foetida gum as a hydrophilic matrix polymer for controlled release preparation. For evaluation as a matrix polymer; characterization of Sterculia foetida gum was done. Viscosity, pH, scanning electronmicrographs were determined. Different formulation aspects considered were: gum concentration (10-40%), particle size (75-420 microm) and type of fillers and those for dissolution studies; pH, and stirring speed were considered. Tablets prepared with Sterculia foetida gum were compared with tablets prepared with Hydroxymethylcellulose K15M. The release rate profiles were evaluated through different kinetic equations: zero-order, first-order, Higuchi, Hixon-Crowell and Korsemeyer and Peppas models. The scanning electronmicrographs showed that the gum particles were somewhat triangular. The viscosity of 1% solution was found to be 950 centipoise and pH was in range of 4-5. Suitable matrix release profile could be obtained at 40% gum concentration. Higher sustained release profiles were obtained for Sterculia foetida gum particles in size range of 76-125 microm. Notable influences were obtained for type of fillers. Significant differences were also observed with rotational speed and dissolution media pH. The in vitro release profiles indicated that tablets prepared from Sterculia foetida gum had higher retarding capacity than tablets prepared with Hydroxymethylcellulose K15M prepared tablets. The differential scanning calorimetry results indicated that there are no interactions of Sterculia foetida gum with diltiazem hydrochloride. It was observed that release of the drug followed through surface erosion and anomalous diffusion. Thus, it could be concluded that Sterculia foetida gum could be used a controlled release matrix polymer.

  9. Use of polysulfone in controlled-release NPK fertilizer formulations.

    PubMed

    Tomaszewska, Maria; Jarosiewicz, Anna

    2002-07-31

    Encapsulation of fertilizers in polymeric coatings is a method used to reduce fertilizer losses and to minimize environmental pollution. Polysulfone was used for a coating preparation for soluble NPK granular fertilizer in controlled-release fertilizer formulations. The coatings were formed by the phase inversion technique (wet method). The influence of the polymer concentration in the film-forming solution on the physical properties of the coatings was examined. The coating structure controls the diffusion of the elements from the interior of the fertilizer granule. It was experimentally confirmed that the use of polysulfone as a coating for a soluble fertilizer decreases the release rate of components. Moreover, the release rate of nutrients from coated granules decreases with the decrease of the coating porosity. In the case of coating with 38.5% porosity, prepared from 13.5% polymer solution after 5 h of test, 100% of NH(4)(+) was released, whereas only 19.0% of NH(4)(+) was released after 5 h for the coating with 11% porosity. In addition, coating of fertilizers leads to improvement of handling properties, and the crushing strength of all coated fertilizers was an average 40% higher than that for uncoated NPK fertilizer.

  10. Polymer-xerogel composites for controlled release wound dressings.

    PubMed

    Costache, Marius C; Qu, Haibo; Ducheyne, Paul; Devore, David I

    2010-08-01

    Many polymers and composites have been used to prepare active wound dressings. These materials have typically exhibited potentially toxic burst release of the drugs within the first few hours followed by a much slower, potentially ineffective drug release rate thereafter. Many of these materials also degraded to produce inflammatory and cytotoxic products. To overcome these limitations, composite active wound dressings were prepared here from two fully biodegradable and tissue compatible components, silicon oxide sol-gel (xerogel) microparticles that were embedded in tyrosine-poly(ethylene glycol)-derived poly(ether carbonate) copolymer matrices. Sustained, controlled release of drugs from these composites was demonstrated in vitro using bupivacaine and mepivacaine, two water-soluble local anesthetics commonly used in clinical applications. By systematically varying independent compositional parameters of the composites, including the hydrophilic:hydrophobic balance of the tyrosine-derived monomers and poly(ethylene glycol) in the copolymers and the porosity, weight ratio and drug content of the xerogels, drug release kinetics approaching zero-order were obtained. Composites with xerogel mass fractions up to 75% and drug payloads as high as 13% by weight in the final material were fabricated without compromising the physical integrity or the controlled release kinetics. The copolymer-xerogel composites thus provided a unique solution for the sustained delivery of therapeutic agents from tissue compatible wound dressings. 2010 Elsevier Ltd. All rights reserved.

  11. Controlled release of ethylene via polymeric films for food packaging

    NASA Astrophysics Data System (ADS)

    Pisano, Roberto; Bazzano, Marco; Capozzi, Luigi Carlo; Ferri, Ada; Sangermano, Marco

    2015-12-01

    In modern fruit supply chain a common method to trigger ripening is to keep fruits inside special chambers and initiate the ripening process through administration of ethylene. Ethylene is usually administered through cylinders with inadequate control of its final concentration in the chamber. The aim of this study is the development of a new technology to accurately regulate ethylene concentration in the atmosphere where fruits are preserved: a polymeric film, containing an inclusion complex of α-cyclodextrin with ethylene, was developed. The complex was prepared by molecular encapsulation which allows the entrapment of ethylene into the cavity of α-cyclodextrin. After encapsulation, ethylene can be gradually released from the inclusion complex and its release rate can be regulated by temperature and humidity. The inclusion complex was dispersed into a thin polymeric film produced by UV-curing. This method was used because is solvent-free and involves low operating temperature; both conditions are necessary to prevent rapid release of ethylene from the film. The polymeric films were characterized with respect to thermal behaviour, crystalline structure and kinetics of ethylene release, showing that can effectively control the release of ethylene within confined volume.

  12. Microparticle dispensers for the controlled release of insect pheromones.

    PubMed

    Stipanovic, Arthur J; Hennessy, Patrick J; Webster, Francis X; Takahashi, Yae

    2004-04-21

    The potential utility of micrometer-sized particles as controlled-release devices for the volatilization of insect pheromones for mating disruption applications is evaluated in this study for two pheromone/model compound systems (codlemone/1-dodecanol and disparlure/1,2-epoxyoctadecane). To expedite the measurement of release rates from these particle devices, two techniques based on thermogravimetric analysis (TGA) have been exploited: isothermal TGA (I-TGA) at elevated temperatures (40-80 degrees C) with N(2) convection and volatilization temperature (VT) by dynamic TGA. A correlation between these two methods has been established. Samples that exhibit a higher VT provide a lower release rate from a particle substrate. Using these techniques, it has been demonstrated that chemical interactions between adsorbed liquids and particle surfaces may play a small role in defining release characteristics under conditions of low surface area, whereas parameters associated with total surface area and micropore structure appear to be much more significant in retarding evaporation for uncoated particles containing an adsorbed liquid. Additional regulation of release rates was achieved by coating the particle systems with water-soluble or water-dispersible polymers. By careful selection of particle porosity and coating composition, it is envisioned that the evaporation rate of pheromones can be tailored to specific insect control applications.

  13. Multifunctional conducting fibres with electrically controlled release of ciprofloxacin.

    PubMed

    Esrafilzadeh, Dorna; Razal, Joselito M; Moulton, Simon E; Stewart, Elise M; Wallace, Gordon G

    2013-08-10

    We hereby present a new method of producing coaxial conducting polymer fibres loaded with an antibiotic drug that can then be subsequently released (or sustained) in response to electrical stimulation. The method involves wet-spinning of poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) fibre, which served as the inner core to the electropolymerised outer shell layer of polypyrrole (Ppy). Ciprofloxacin hydrochloride (Cipro) was selected as the model drug and as the dopant in the Ppy synthesis. The release of Cipro in phosphate buffered saline (PBS) from the fibres was controlled by switching the redox state of Ppy.Cipro layer. Released Cipro under passive and stimulated conditions were tested against Gram positive (Streptococcus pyogenes) and Gram negative (Escherichia coli) bacteria. Significant inhibition of bacterial growth was observed against both strains tested. These results confirm that Cipro retains antibacterial properties during fibre fabrication and electrochemically controlled release. In vitro cytotoxicity testing utilising the neural B35 cell line confirmed the cytocompatibility of the drug loaded conducting fibres. Electrical conductivity, cytocompatibility and tuning release profile from this flexible fibre can lead to promising bionic applications such as neuroprosthetics and localised drug delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Intrathecal Morphine Versus Extended-Release Epidural Morphine for Postoperative Pain Control in Pediatric Patients Undergoing Posterior Spinal Fusion.

    PubMed

    Cohen, Mindy; Zuk, Jeannie; McKay, Nancy; Erickson, Mark; Pan, Zhaoxing; Galinkin, Jeffrey

    2017-06-01

    Posterior spinal fusion for scoliosis is one of the most painful elective pediatric surgeries. Good postoperative pain control allows early ambulation and return of ability to tolerate oral intake. Options for analgesia in this patient population are suboptimal. We hypothesized that extended-release epidural morphine (EREM) would provide better pain control and less adverse effects compared to intrathecal (IT) morphine. The primary outcome was total IV morphine consumption during 0-48 hours postoperatively. Secondary outcomes included time until first patient-controlled analgesia (PCA) demand, pain scores, and adverse opioid effects. After institutional review board approval, 71 subjects undergoing posterior spinal fusion for idiopathic scoliosis completed the study. The subjects were randomly allocated to 7.5 μg/kg IT morphine or 150 μg/kg EREM. The final IT morphine and EREM groups contained 37 and 34 subjects, respectively. Postoperative pain was treated with morphine PCA, ketorolac, oral oxycodone, and acetaminophen. Morphine consumption, pain scores, nausea and vomiting, pruritus, and respiratory depression were measured every 4 hours. Parents completed a caregiver questionnaire about their child's pain control regimen after the first postoperative day. There was no difference in total morphine consumption over the first 48 hours between subjects in the EREM and IT morphine groups: median (range) 42.2 (5.5-123.0) and 34.0 (4.5-128.8) mg, respectively (P = .27). EREM and IT morphine groups had no difference in time until first PCA demand. Pain scores were no different between the groups from 8 to 24 hours after surgery. Compared to IT morphine, EREM subjects had lower pain scores from 28 to 36 hours after surgery. The reported incidence of pruritus was lower in the EREM subjects. There was no difference in total morphine consumption or time until first PCA demand between the EREM and IT morphine groups. EREM provides a longer duration of analgesia after

  15. Tailoring liquid crystalline lipid nanomaterials for controlled release of macromolecules.

    PubMed

    Bisset, Nicole B; Boyd, Ben J; Dong, Yao-Da

    2015-11-10

    Lipid-based liquid crystalline materials are being developed as drug delivery systems. However, the use of these materials for delivery of large macromolecules is currently hindered by the small size of the water channels in these structures limiting control over diffusion behaviour. The addition of the hydration-modulating agent, sucrose stearate, to phytantriol cubic phase under excess water conditions incrementally increased the size of these water channels. Inclusion of oleic acid enabled further control of swelling and de-swelling of the matrix via a pH triggerable system where at low pH the hexagonal phase is present and at higher pH the cubic phase is present. Fine control over the release of various sized model macromolecules is demonstrated, indicating future application to controlled loading and release of large macromolecules such as antibodies. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Toxicology and characteristics of fatal oxycodone toxicity cases in New South Wales, Australia 1999-2008.

    PubMed

    Darke, Shane; Duflou, Johan; Torok, Michelle

    2011-05-01

    All cases of fatal oxycodone toxicity presenting to the New South Wales Department of Forensic Medicine over the period January 1, 1999, to December 31, 2008, were retrieved. A total of 70 cases were identified. The mean age was 48.9 years, 58.6% were men, 21.4% were suicides, and in 30% oxycodone had not been prescribed to the decedent. Injecting drug users constituted 27.1% of cases, and oxycodone tablets were injected immediately prior to death by 21.4%. The mean blood oxycodone concentration was 0.40 mg/L (range 0.06-53.00 mg/L). In all cases, psychoactive substances other than oxycodone were also detected, most frequently hypnosedatives (68.6%), other opioids (54.3%), antidepressants (41.4%), and alcohol (32.9%). Preexisting systemic disease was common: cardiovascular (64.2%), pulmonary (49.3%), hepatic (66.7%), and renal (43.9%).

  17. Controlled release of molecular components of dendrimer/bioactive complexes

    DOEpatents

    Segalman, Daniel J.; Wallace, J. Shield

    1998-01-01

    A method for releasing molecules (guest molecules) from the matrix formed by the structure of another molecule (host molecule) in a controllable manner has been invented. This method has many applications in science and industry. In addition, applications based on such molecular systems may revolutionize significant areas of medicine, in particular the treatment of cancer and of viral infection. Similar effects can also be obtained by controlled fragmentation of a source molecule, where the molecular fragments form the active principle.

  18. Controlled release of molecular components of dendrimer/bioactive complexes

    DOEpatents

    Segalman, D.J.; Wallace, J.S.

    1998-08-18

    A method for releasing molecules (guest molecules) from the matrix formed by the structure of another molecule (host molecule) in a controllable manner has been invented. This method has many applications in science and industry. In addition, applications based on such molecular systems may revolutionize significant areas of medicine, in particular the treatment of cancer and of viral infection. Similar effects can also be obtained by controlled fragmentation of a source molecule, where the molecular fragments form the active principle. 13 figs.

  19. Polyelectrolyte complexes stabilize and controllably release vascular endothelial growth factor.

    PubMed

    Huang, Min; Vitharana, Samadhi N; Peek, Laura J; Coop, Tina; Berkland, Cory

    2007-05-01

    Angiogenesis has long been a desired therapeutic approach to improve clinical outcomes of conditions typified by ischemia. Vascular endothelial growth factor (VEGF) has demonstrated the ability to generate new blood vessels in vivo, but trials using intravenous delivery have not yet produced clinical success. Localized, sustained delivery of VEGF has been proven necessary to generate blood vessels as demonstrated by implantable, controlled release devices. Ultimately, nanoparticles delivered by intravenous injection may be designed to accumulate in target tissues and sustain the local VEGF concentration; however, injectable nanosuspensions that control the release of stabilized VEGF must first be developed. In this study, we utilize the heparin binding domain of VEGF to bind the polyanion dextran sulfate, resulting in an enhanced thermal stability of VEGF. Coacervation of the VEGF-bound dextran sulfate with selected polycations (chitosan, polyethylenimine, or poly-L-lysine) produced nanoparticles approximately 250 nm in diameter with high VEGF encapsulation efficiency (50-85%). Release of VEGF from these formulations persisted for >10 days and maintained high VEGF activity as determined by ELISA and a mitogenic bioassay. Chitosan-dextran sulfate complexes were preferred because of their biodegradability, desirable particle size ( approximately 250 nm), entrapment efficiency ( approximately 85%), controlled release (near linear for 10 days), and mitogenic activity.

  20. Prenatal Oxycodone Exposure Alters CNS Endothelin Receptor Expression in Neonatal Rats.

    PubMed

    Devarapalli, M; Leonard, M; Briyal, S; Stefanov, G; Puppala, B L; Schweig, L; Gulati, A

    2016-05-01

    Prenatal opioid exposure such as oxycodone is linked to significant adverse effects on the developing brain. Endothelin (ET) and its receptors are involved in normal development of the central nervous system. Opioid tolerance and withdrawal are mediated through ET receptors. It is possible that adverse effect of oxycodone on the developing brain is mediated through ET receptors. We evaluated brain ETA and ETB receptor expression during postnatal development in rats with prenatal oxycodone exposure. Timed pregnant Sprague-Dawley rats received either oxycodone or placebo throughout gestation. After birth, male rat pups were sacrificed on postnatal day (PND) 1, 7, 14 or 28. Brain ETA and ETB receptor expression was determined by Western blot analysis. Oxycodone pups compared to placebo demonstrated congenital malformations of the face, mouth, and vertebrae at the time of birth [4/69 (5.7%) vs. 0/60 (0%); respectively] and intrauterine growth retardation [10/69 (15%) vs. 2/60 (3.3%); respectively]. On PND 28, oxycodone pups compared to placebo had lower body and kidney weight. ETA receptor expression in the oxycodone group was significantly higher compared to placebo on PND 1 (p=0.035), but was similar on PND 7, 14, or 28. ETB receptor expression decreased in oxycodone compared to placebo on PND 1 and 7 (p=0.001); and increased on PND 28 (p=0.002), but was similar on PND 14. Oxycodone-exposed rat pups had lower birth weight and postnatal weight gain and greater congenital malformations. ETB receptor expression is altered in the brain of oxycodone-treated rat pups indicating a possible delay in CNS development.

  1. Oxycodone physical dependence and its oral self-administration in C57BL/6J mice.

    PubMed

    Enga, Rachel M; Jackson, Asti; Damaj, M Imad; Beardsley, Patrick M

    2016-10-15

    Abuse of prescription opioids, such as oxycodone, has markedly increased in recent decades. While oxycodone's antinociceptive effects have been detailed in several preclinical reports, surprisingly few preclinical reports have elaborated its abuse-related effects. This is particularly surprising given that oxycodone has been in clinical use since 1917. In a novel oral operant self-administration procedure, C57BL/6J mice were trained to self-administer water before introducing increasing concentrations of oxycodone (0.056-1.0mg/ml) under post-prandial conditions during daily, 3-h test sessions. As the concentration of oxycodone increased, the numbers of deliveries first increased, then decreased in an inverted U-shape fashion characteristic of the patterns of other drugs self-administered during limited access conditions. After post-prandial conditions were removed, self-administration at the highest concentration was maintained suggesting oral oxycodone served as a positive reinforcer. In other mice, using a novel regimen of physical dependence, mice were administered increasing doses of oxycodone (9.0-33.0mg/kg, s.c.) over 9 days, challenged with naloxone (0.1-10.0mg/kg, s.c.), and then observed for 30min. Naloxone dose-dependently increased the observed number of somatic signs of withdrawal, suggesting physical dependence of oxycodone was induced under this regimen. This is the first report demonstrating induction of oral operant self-administration of oxycodone and dose-dependent precipitations of oxycodone withdrawal in C57BL/6J mice. The use of oral operant self-administration as well as the novel physical dependence regimen provides useful approaches to further examine the abuse- and dependence-related effects of this highly abused prescription opioid.

  2. Ultra-low-dose naltrexone reduces the rewarding potency of oxycodone and relapse vulnerability in rats.

    PubMed

    Leri, Francesco; Burns, Lindsay H

    2005-10-01

    Ultra-low-dose opioid antagonists have been shown to enhance opioid analgesia and alleviate opioid tolerance and dependence. Our present studies in male Sprague-Dawley rats assessed the abuse potential of oxycodone+ultra-low-dose naltrexone (NTX) versus oxycodone alone. The lowest NTX dose (1 pg/kg/infusion), but not slightly higher doses (10 and 100 pg/kg/infusion), enhanced oxycodone (0.1 mg/kg/infusion) intravenous self-administration, suggesting a reduced rewarding potency per infusion. During tests of reinstatement performed in extinction conditions, co-self-administration of any of these three NTX doses significantly reduced drug-seeking precipitated by priming injections of oxycodone (0.25 mg/kg, s.c.), a drug-conditioned cue, or foot-shock stress. During self-administration on a progressive-ratio schedule, animals self-administering oxycodone (0.1 mg/kg/infusion)+NTX (1 pg/kg/infusion) reached a "break-point" sooner and showed a trend toward less responding compared to rats self-administering oxycodone alone (0.1 mg/kg/infusion). In the final experiment, the addition of ultra-low-dose NTX (10 pg/kg, s.c.) enhanced the acute stimulatory effect of oxycodone (1 mg/kg, s.c.), as well as locomotor sensitization produced by repeated oxycodone administration (7 x 1 mg/kg, s.c.). In summary, this work shows that ultra-low-dose NTX co-treatment augments the locomotor effects of oxycodone as it enhances opioid analgesia, but reduces oxycodone's rewarding potency and subsequent vulnerability to relapse.

  3. Controlled-release systems for the insect growth regulator pyriproxyfen.

    PubMed

    Schwartz, Liliana; Wolf, David; Markus, Arie; Wybraniec, Sławomir; Wiesman, Zeev

    2003-09-24

    A simple technique was developed for the production of controlled-release systems (CRSs) for pyriproxyfen, an insect growth regulator active against the larvae of Culex pipiens, the most common species of mosquito found in developed countries. The CRSs consisted of a spongy core material encapsulated in a coating of a polyurethane or polyurea hydrogel, into which the active ingredient had been incorporated. The coating also included a surfactant to improve the low solubility in water of pyriproxyfen. The light core material enabled the CRS to float on the water surface, where the mosquitoe larvae are found. The type and amount of the polymeric coating and the amount of surfactant influenced the release profiles into water of the active ingredient. The release profiles of the CRSs were adjusted to the life cycle of the C. pipiens mosquito in order to obtain their optimal activity on the eighth day, which corresponds to the time of larval maturity.

  4. Carbon monoxide – physiology, detection and controlled release

    PubMed Central

    Heinemann, Stefan H.; Hoshi, Toshinori; Westerhausen, Matthias

    2014-01-01

    Carbon monoxide (CO) is increasingly recognized as a cell-signalling molecule akin to nitric oxide (NO). CO has attracted particular attention as a potential therapeutic agent because of its reported anti-hypertensive, anti-inflammatory and cell-protective effects. We discuss recent progress in identifying new effector systems and elucidating the mechanisms of action of CO on, e.g., ion channels, as well as the design of novel methods to monitor CO in cellular environments. We also report on recent developments in the area of CO-releasing molecules (CORMs) and materials for controlled CO application. Novel triggers for CO release, metal carbonyls and degradation mechanisms of CORMs, are highlighted. In addition, potential formulations of CORMs for targeted CO release are discussed. PMID:24556640

  5. Intelligent type controlled release systems by radiation techniques

    NASA Astrophysics Data System (ADS)

    Kaetsu, Isao; Uchida, Kumao; Shindo, Hironori; Gomi, Seiji; Sutani, Kouichi

    1999-06-01

    Intelligent controlled release systems have been designed and constructed. The systems have a sensor-actuator gate consisting of polyelectrolyte hydrogel layer with immobilized enzymes inside fine holes of polyethylene terephthalate (PET) film and silicon wafer as base materials. Excimer-laser or ion-beam irradiation was used for the etching of holes in PET film and photo-lithography was used for the etching of silicon wafer. U.V. and γ-ray irradiations were used for the polymerization and immobilization of electrolyte layers in the holes. Various kinds of signal responsive release systems such as pH responsive, substrate responsive, Ca 2+ responsive, photo-responsive and electric field responsive systems have been developed using those techniques. Some integrated systems have been designed and constructed by combination of unit systems in series and in parallel and proved the selective signal transfer and the successive signal responsive release functions.

  6. HIV risk behavior in opioid dependent adults seeking detoxification treatment: an exploratory comparison of heroin and oxycodone users.

    PubMed

    Meade, Christina S; McDonald, Leah J; Weiss, Roger D

    2009-01-01

    Heroin users are at high risk for HIV infection, but little is known about HIV risk in oxycodone users. This study examined HIV risk behaviors in heroin (n = 27) and oxycodone (n = 23) users seeking inpatient detoxification at a private psychiatric hospital. Drug use histories were similar, except oxycodone users used marijuana more frequently. Injection drug risk occurred exclusively among heroin users. The rates of sexual activity (66%), unprotected intercourse (69%), sex while intoxicated (74%), and sex with strangers (24%) were similar, but more oxycodone users had multiple partners (39% vs. 6%, p < .05). HIV prevention efforts should target both heroin and oxycodone users.

  7. Optogenetic Control of Serotonin and Dopamine Release in Drosophila Larvae

    PubMed Central

    2014-01-01

    Optogenetic control of neurotransmitter release is an elegant method to investigate neurobiological mechanisms with millisecond precision and cell type-specific resolution. Channelrhodopsin-2 (ChR2) can be expressed in specific neurons, and blue light used to activate those neurons. Previously, in Drosophila, neurotransmitter release and uptake have been studied after continuous optical illumination. In this study, we investigated the effects of pulsed optical stimulation trains on serotonin or dopamine release in larval ventral nerve cords. In larvae with ChR2 expressed in serotonergic neurons, low-frequency stimulations produced a distinct, steady-state response while high-frequency patterns were peak shaped. Evoked serotonin release increased with increasing stimulation frequency and then plateaued. The steady-state response and the frequency dependence disappeared after administering the uptake inhibitor fluoxetine, indicating that uptake plays a significant role in regulating the extracellular serotonin concentration. Pulsed stimulations were also used to evoke dopamine release in flies expressing ChR2 in dopaminergic neurons and similar frequency dependence was observed. Release due to pulsed optical stimulations was modeled to determine the uptake kinetics. For serotonin, Vmax was 0.54 ± 0.07 μM/s and Km was 0.61 ± 0.04 μM; and for dopamine, Vmax was 0.12 ± 0.03 μM/s and Km was 0.45 ± 0.13 μM. The amount of serotonin released per stimulation pulse was 4.4 ± 1.0 nM, and the amount of dopamine was 1.6 ± 0.3 nM. Thus, pulsed optical stimulations can be used to mimic neuronal firing patterns and will allow Drosophila to be used as a model system for studying mechanisms underlying neurotransmission. PMID:24849718

  8. Photocatalytic Degradation of Cell Membrane Coatings for Controlled Drug Release.

    PubMed

    Rao, Lang; Meng, Qian-Fang; Huang, Qinqin; Liu, Pei; Bu, Lin-Lin; Kondamareddy, Kiran Kumar; Guo, Shi-Shang; Liu, Wei; Zhao, Xing-Zhong

    2016-06-01

    Biomimetic cell-membrane-camouflaged particles with desirable features have been widely used for various biomedical applications. However, there are few reports on employing these particles for cancer drug delivery due to the failure of the membrane coatings to be efficiently degraded in the tumor microenvironment which hampers the drug release. In this work, core-shell SiO2 @TiO2 nanoparticles with enhanced photocatalytic activity are used for controlled degradation of surface erythrocyte membrane coatings. The antitumor drug docetaxel is encapsulated into nanocarriers to demonstrate the controlled drug release under ultraviolet irradiation, and the drug-loaded nanoparticles are further used for enhanced cancer cell therapy. Here, a simple but practical method for degradation of cell membrane coatings is presented, and a good feasibility of using cell membrane-coated nanocarriers for controlled drug delivery is demonstrated.

  9. Sustainable practices for fertilizer use through controlled release techniques

    NASA Astrophysics Data System (ADS)

    Faez, Roselena; Messa, Lucas; Froes, José; Souza, Claudinei

    2015-04-01

    Controlled release fertilizers are efficient tools that increase the sustainability of agricultural practices. However, the biodegradability of the matrices and the determination of the release into soil still require some investigation. This work describes the preparation of potassium-containing microspheres based on chitosan- montmorillonite clay as fertilizer double coated. The release profile in water (ion conductivity measurement) and soil (ion movement performed with time-domain reflectometry (TDR) technique) were evaluated. The potassium-containing microspheres were placed in a 7.5-L container filled with soil (Typic dystrophic LVd). The container was prepared with a water drainage system consisting of a thin layer of gravel at the bottom, which was followed by a geotextile fabric to prevent the loss of soil. The container was filled with soil (9 kg) in layers of 0.05 m to simulate the original bulk density of 1.30 g.cm-3. Each container received 4 g of microspheres placed at a single spot. They were placed at a depth of 10 cm. The fertilizer release was monitored using three electromagnetic probes for TDR that consisted of three continuous metal rods of 20 cm, which were in contact with the material and can be used to estimate the moisture and electrical conductivity. One probe was installed at the center of the container, which meant the rod was in contact with the microspheres in the soil. The other two probes were installed 5 cm from the central probe, and they were only in contact with the soil. Therefore, the purpose of these probes was to monitor the lateral displacement of the fertilizer from the microspheres in the soil. The release in water is fast than in soil, since the total amount of fertilizer in water was delivery during only one week and in soil during 60 days the fertilizer still continue drifting. The composite based on chitosan biopolymer as controlled release material is an efficient method to monitor the fertilizer consumption.

  10. Cellulose, chitosan, and keratin composite materials. Controlled drug release.

    PubMed

    Tran, Chieu D; Mututuvari, Tamutsiwa M

    2015-02-03

    A method was developed in which cellulose (CEL) and/or chitosan (CS) were added to keratin (KER) to enable [CEL/CS+KER] composites to have better mechanical strength and wider utilization. Butylmethylimmidazolium chloride ([BMIm(+)Cl(-)]), an ionic liquid, was used as the sole solvent, and because the [BMIm(+)Cl(-)] used was recovered, the method is green and recyclable. Fourier transform infrared spectroscopy results confirm that KER, CS, and CEL remain chemically intact in the composites. Tensile strength results expectedly show that adding CEL or CS into KER substantially increases the mechanical strength of the composites. We found that CEL, CS, and KER can encapsulate drugs such as ciprofloxacin (CPX) and then release the drug either as a single or as two- or three-component composites. Interestingly, release rates of CPX by CEL and CS either as a single or as [CEL+CS] composite are faster and independent of concentration of CS and CEL. Conversely, the release rate by KER is much slower, and when incorporated into CEL, CS, or CEL+CS, it substantially slows the rate as well. Furthermore, the reducing rate was found to correlate with the concentration of KER in the composites. KER, a protein, is known to have secondary structure, whereas CEL and CS exist only in random form. This makes KER structurally denser than CEL and CS; hence, KER releases the drug slower than CEL and CS. The results clearly indicate that drug release can be controlled and adjusted at any rate by judiciously selecting the concentration of KER in the composites. Furthermore, the fact that the [CEL+CS+KER] composite has combined properties of its components, namely, superior mechanical strength (CEL), hemostasis and bactericide (CS), and controlled drug release (KER), indicates that this novel composite can be used in ways which hitherto were not possible, e.g., as a high-performance bandage to treat chronic and ulcerous wounds.

  11. Cellulose, Chitosan, and Keratin Composite Materials. Controlled Drug Release

    PubMed Central

    2015-01-01

    A method was developed in which cellulose (CEL) and/or chitosan (CS) were added to keratin (KER) to enable [CEL/CS+KER] composites to have better mechanical strength and wider utilization. Butylmethylimmidazolium chloride ([BMIm+Cl–]), an ionic liquid, was used as the sole solvent, and because the [BMIm+Cl–] used was recovered, the method is green and recyclable. Fourier transform infrared spectroscopy results confirm that KER, CS, and CEL remain chemically intact in the composites. Tensile strength results expectedly show that adding CEL or CS into KER substantially increases the mechanical strength of the composites. We found that CEL, CS, and KER can encapsulate drugs such as ciprofloxacin (CPX) and then release the drug either as a single or as two- or three-component composites. Interestingly, release rates of CPX by CEL and CS either as a single or as [CEL+CS] composite are faster and independent of concentration of CS and CEL. Conversely, the release rate by KER is much slower, and when incorporated into CEL, CS, or CEL+CS, it substantially slows the rate as well. Furthermore, the reducing rate was found to correlate with the concentration of KER in the composites. KER, a protein, is known to have secondary structure, whereas CEL and CS exist only in random form. This makes KER structurally denser than CEL and CS; hence, KER releases the drug slower than CEL and CS. The results clearly indicate that drug release can be controlled and adjusted at any rate by judiciously selecting the concentration of KER in the composites. Furthermore, the fact that the [CEL+CS+KER] composite has combined properties of its components, namely, superior mechanical strength (CEL), hemostasis and bactericide (CS), and controlled drug release (KER), indicates that this novel composite can be used in ways which hitherto were not possible, e.g., as a high-performance bandage to treat chronic and ulcerous wounds. PMID:25548871

  12. Controlled release of 5-fluorouracil from microporous zeolites.

    PubMed

    Spanakis, Marios; Bouropoulos, Nikolaos; Theodoropoulos, Dimitrios; Sygellou, Lamprini; Ewart, Sinead; Moschovi, Anastasia Maria; Siokou, Angeliki; Niopas, Ioannis; Kachrimanis, Kyriakos; Nikolakis, Vladimiros; Cox, Paul A; Vizirianakis, Ioannis S; Fatouros, Dimitrios G

    2014-01-01

    Zeolite particles with different pore diameter and particle size were loaded with the model anticancer drug 5-fluorouracil. The loaded zeolites were characterized by means of SEM, XRD, DSC, XPS, N2 physisorption and FT-IR. Higher loading of 5-FU was observed for NaX-FAU than BEA. Release studies were carried out in HCl 0.1N. Release of 5-FU from NaX-FAU showed exponential-type behaviour with the drug fully released within 10 min. In the case of BEA, the kinetics of 5-FU shows a multi-step profile with prolonged release over time. Molecular dynamics simulations showed that diffusion of the drug molecule through the BEA framework is lower than for NaX-FAU due to increased van der Waals interaction between the drug and the framework. The effect of zeolitic particles on the viability of Caco-2 monolayers showed that the NaX-FAU particles cause a reduction of cell viability in a more pronounced way compared with the BEA particles. This article describes zeolite-based nanoparticles in generating time-controlled release of 5-FU from zeolite preparations for anti-cancer therapy. © 2013.

  13. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications

    NASA Astrophysics Data System (ADS)

    Yassine, Omar; Zaher, Amir; Li, Er Qiang; Alfadhel, Ahmed; Perez, Jose E.; Kavaldzhiev, Mincho; Contreras, Maria F.; Thoroddsen, Sigurdur T.; Khashab, Niveen M.; Kosel, Jurgen

    2016-06-01

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads.

  14. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications.

    PubMed

    Yassine, Omar; Zaher, Amir; Li, Er Qiang; Alfadhel, Ahmed; Perez, Jose E; Kavaldzhiev, Mincho; Contreras, Maria F; Thoroddsen, Sigurdur T; Khashab, Niveen M; Kosel, Jurgen

    2016-06-23

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads.

  15. Highly Efficient Thermoresponsive Nanocomposite for Controlled Release Applications

    PubMed Central

    Yassine, Omar; Zaher, Amir; Li, Er Qiang; Alfadhel, Ahmed; Perez, Jose E.; Kavaldzhiev, Mincho; Contreras, Maria F.; Thoroddsen, Sigurdur T.; Khashab, Niveen M.; Kosel, Jurgen

    2016-01-01

    Highly efficient magnetic release from nanocomposite microparticles is shown, which are made of Poly (N-isopropylacrylamide) hydrogel with embedded iron nanowires. A simple microfluidic technique was adopted to fabricate the microparticles with a high control of the nanowire concentration and in a relatively short time compared to chemical synthesis methods. The thermoresponsive microparticles were used for the remotely triggered release of Rhodamine (B). With a magnetic field of only 1 mT and 20 kHz a drug release of 6.5% and 70% was achieved in the continuous and pulsatile modes, respectively. Those release values are similar to the ones commonly obtained using superparamagnetic beads but accomplished with a magnetic field of five orders of magnitude lower power. The high efficiency is a result of the high remanent magnetization of the nanowires, which produce a large torque when exposed to a magnetic field. This causes the nanowires to vibrate, resulting in friction losses and heating. For comparison, microparticles with superparamagnetic beads were also fabricated and tested; while those worked at 73 mT and 600 kHz, no release was observed at the low field conditions. Cytotoxicity assays showed similar and high cell viability for microparticles with nanowires and beads. PMID:27335342

  16. Thermally controlled protein release from gelatin dextran hydrogels

    NASA Astrophysics Data System (ADS)

    Aso, Y.; Yoshioka, S.; Nakai, Y.; Kojima, S.

    1999-06-01

    Biodegradable hydrogels in which drug release was controlled by sol-gel transition were prepared. Gelatin was used as a component because it exhibits sol-gel transition in response to temperature changes. Glycidyl methacrylated (GMA) dextran was crosslinked by low dose γ-irradiation in the presence of gelatin and the model drugs, β-galactosidase ( β-GA), bovine serum albumin (BSA) or 5-fluorouracil (5-FU). The enzyme activity of β-GA remained greater than 95% after irradiation. Temperature-responsive release of β-GA and BSA resulted from the sol-gel transition of gelatin. Sol-gel transition was confirmed by the temperature dependence of the spin-spin relaxation time of the gel polymer protons. The protein release rate was affected by both the degree of GMA substitution and the gelatin concentration. Desired release rate could be achieved by adjusting these factors. The release rate of 5-FU was not affected by the sol-gel transition of gelatin.

  17. Quantitative sensory tests fairly reflect immediate effects of oxycodone in chronic low-back pain.

    PubMed

    Schliessbach, Jürg; Siegenthaler, Andreas; Bütikofer, Lukas; Vuilleumier, Pascal; Jüni, Peter; Arendt-Nielsen, Lars; Curatolo, Michele

    2017-08-09

    Quantitative sensory tests (QST) can be used for profiling anti-nociceptive effects of analgesics. However, anti-nociceptive effects detected by QST are not necessarily associated with analgesic effects in pain patients. As part of a large investigation on low back pain, this paper describes the immediate analgesic and anti-nociceptive effects of oxycodone in chronic low-back pain and ranks different QST according to their ability to reflect this effect. The results are expected to support the selection of QST for future studies on potential novel opioid agonists in human pain. In this randomized, placebo-controlled and double-blinded cross-over study, 50 patients with chronic low-back pain received a single oral dose of oxycodone 15mg or active placebo, and underwent multiple QST testing. The intensity of low-back pain was recorded during 2h. The areas under the ROC curves and 95% confidence intervals were determined, whereby responder status (≥30% pain reduction) was set as reference variable and changes in QST from baseline were set as classifiers. Significant analgesic effect on low-back pain as well as anti-nociceptive effects for almost all QST parameters were observed. The QST with the highest area under the curve were heat pain detection threshold (0.65, 95%-CI 0.46 to 0.83), single-stimulus electrical pain threshold (0.64, 95%-CI 0.47 to 0.80) and pressure pain detection threshold (0.63, 95%-CI 0.48 to 0.79). The results suggest that anti-nociceptive effects assessed by QST fairly reflect clinical efficacy of oxycodone on low-back pain. Pressure pain detection threshold, heat pain detection threshold and single-stimulus electrical pain threshold may be more suitable to sort out potential non-responders rather than identifying potential responders to opioid medication. Future pre-clinical human research may consider these results when investigating the analgesic effect of opioid agonists by means of QST. Copyright © 2017 Scandinavian Association for the

  18. Controlled Release of Agrochemicals Intercalated into Montmorillonite Interlayer Space

    PubMed Central

    2014-01-01

    Periodic application of agrochemicals has led to high cost of production and serious environmental pollution. In this study, the ability of montmorillonite (MMT) clay to act as a controlled release carrier for model agrochemical molecules has been investigated. Urea was loaded into MMT by a simple immersion technique while loading of metalaxyl was achieved by a rotary evaporation method. The successful incorporation of the agrochemicals into the interlayer space of MMT was confirmed by several techniques, such as, significant expansion of the interlayer space, reduction of Barrett-Joyner-Halenda (BJH) pore volumes and Brunauer-Emmett-Teller (BET) surface areas, and appearance of urea and metalaxyl characteristic bands on the Fourier-transform infrared spectra of the urea loaded montmorillonite (UMMT) and metalaxyl loaded montmorillonite (RMMT) complexes. Controlled release of the trapped molecules from the matrix was done in water and in the soil. The results reveal slow and sustained release behaviour for UMMT for a period of 10 days in soil. For a period of 30 days, MMT delayed the release of metalaxyl in soil by more than 6 times. It is evident that MMT could be used to improve the efficiency of urea and metalaxyl delivery in the soil. PMID:24696655

  19. A new biodegradable polythiourethane as controlled release matrix polymer.

    PubMed

    Campiñez, M D; Ferris, C; de Paz, M V; Aguilar-de-Leyva, A; Galbis, J; Caraballo, I

    2015-03-01

    The main aim of this paper is the synthesis and characterization of a new linear functional biodegradable polythiourethane-d,l-1,4-dithiothreitol-hexamethylene diisocyanate [PTU(DTT-HMDI)]. The SeDeM diagram has been obtained to investigate its suitability to be processed through a direct compression process. Furthermore, the ability of this polymer to act as controlled release matrix forming excipient has been studied. Four batches of matrices containing 10-40% of polymer and theophylline anhydrous as model drug have been manufactured. Release studies have been carried out using the paddle method and the polymer percolation threshold has been estimated. The principal parameters of the SeDeM Expert system, such as the parametric profile (mean radius) and the good compression index (IGC=4.59) for the polymer are very close to the values considered as adequate for direct compression even with no addition of flow agents. Furthermore, the results of the drug release studies show a high ability of the polymer to control the drug release. The excipient percolation threshold has been estimated between 20% and 30% w/w of polymer.

  20. pH-controlled drug release for dental applications

    NASA Astrophysics Data System (ADS)

    Wironen, John Francis

    A large proportion of the dental fillings replaced at present are revised because of the perceived presence of a recurrent caries under or adjacent to the restoration. Many of these perceived caries may not exist, while others may go undetected. This work describes the preparation of drug loaded polymer microspheres that sense the presence of the bacteria that cause caries by the associated presence of acid by-products of digestion. These microspheres are designed to swell and release their antimicrobial drugs once the pH drops to a level that would normally cause caries. The preparation of the microspheres as well as their loading with potassium fluoride, chlorhexidine digluconate, chlorhexidine dihydrochloride, chlorhexidine diacetate, and tetracycline hydrochloride are described. A detailed study of the controlled release behavior of fluoride as a function of polymer composition and pH is presented first. A study of the release kinetics of potassium fluoride, chlorhexidine digluconate, diacetate, dihydrochloride, and tetracycline hydrochloride as a function of pH in the same polymer system is then presented. Additional studies of the swelling kinetics of chlorhexidine-loaded microspheres in various pH buffers are discussed with special reference to correlations with the controlled-release data. Finally, an experiment in which the microspheres are tested in an in vitro bacteria model that includes Streptococcus mutans is presented and discussed in detail.

  1. Controlled release of agrochemicals intercalated into montmorillonite interlayer space.

    PubMed

    Wanyika, Harrison

    2014-01-01

    Periodic application of agrochemicals has led to high cost of production and serious environmental pollution. In this study, the ability of montmorillonite (MMT) clay to act as a controlled release carrier for model agrochemical molecules has been investigated. Urea was loaded into MMT by a simple immersion technique while loading of metalaxyl was achieved by a rotary evaporation method. The successful incorporation of the agrochemicals into the interlayer space of MMT was confirmed by several techniques, such as, significant expansion of the interlayer space, reduction of Barrett-Joyner-Halenda (BJH) pore volumes and Brunauer-Emmett-Teller (BET) surface areas, and appearance of urea and metalaxyl characteristic bands on the Fourier-transform infrared spectra of the urea loaded montmorillonite (UMMT) and metalaxyl loaded montmorillonite (RMMT) complexes. Controlled release of the trapped molecules from the matrix was done in water and in the soil. The results reveal slow and sustained release behaviour for UMMT for a period of 10 days in soil. For a period of 30 days, MMT delayed the release of metalaxyl in soil by more than 6 times. It is evident that MMT could be used to improve the efficiency of urea and metalaxyl delivery in the soil.

  2. Formulation and Evaluation of Controlled Release Floating Microballoons of Stavudine.

    PubMed

    Vidyadhara, Suryadevara; Sasidhar, Reddyvalam Lankapalli; Balakrishna, Talamanchi; Balaji, Boyapati; Amrutha, Ravi

    2015-01-01

    The aim of this study was to formulate and evaluate stavudine floating microballoons for controlled drug release. Initially, the drug-loaded low-density granular pellets were prepared with hydroxypropyl methylcellulose E5 grade and by using isopropyl alcohol as a granulating fluid. Further, the low-density granular pellets were subjected to microencapsulation by an emulsion evaporation technique using ethyl cellulose 7 cps and Eudragit S 100 as coating polymers and 1% w/v polyethylene glycol 400 as aqueous phase. The prepared microballoons were characterized for their particle size analysis, angle of repose, and compressibility index. The in vitro release studies were performed in 0.1 N HCl as medium. The prepared microballoons were free-flowing and spherical in shape. From all the formulations, F5E and F5F can be considered as promising controlled release floating microballoons of stavudine providing first-order release over a period of 12 hours, with a minimum floating lag time of 1 minute. It was found that the ratio of the drug & polymer, stirring speed, and concentration of surfactant were the most significant variables which influenced the size of the stavudine microballoons under the applied experimental conditions.

  3. Formulation and Evaluation of Controlled Release Floating Microballoons of Stavudine

    PubMed Central

    Vidyadhara, Suryadevara; Sasidhar, Reddyvalam Lankapalli; Balakrishna, Talamanchi; Balaji, Boyapati; Amrutha, Ravi

    2015-01-01

    The aim of this study was to formulate and evaluate stavudine floating microballoons for controlled drug release. Initially, the drug-loaded low-density granular pellets were prepared with hydroxypropyl methylcellulose E5 grade and by using isopropyl alcohol as a granulating fluid. Further, the low-density granular pellets were subjected to microencapsulation by an emulsion evaporation technique using ethyl cellulose 7 cps and Eudragit S 100 as coating polymers and 1% w/v polyethylene glycol 400 as aqueous phase. The prepared microballoons were characterized for their particle size analysis, angle of repose, and compressibility index. The in vitro release studies were performed in 0.1 N HCl as medium. The prepared microballoons were free-flowing and spherical in shape. From all the formulations, F5E and F5F can be considered as promising controlled release floating microballoons of stavudine providing first-order release over a period of 12 hours, with a minimum floating lag time of 1 minute. It was found that the ratio of the drug & polymer, stirring speed, and concentration of surfactant were the most significant variables which influenced the size of the stavudine microballoons under the applied experimental conditions. PMID:26839847

  4. Controlled-release injectable microemulsions: recent advances and potential opportunities.

    PubMed

    Dubey, Rajesh

    2014-02-01

    Controlled-release injectable (CRI) formulations hold significant value for several indications. However, there have been very few successful developments and approvals due to various challenges that include limited polymer options, drug-excipient process incompatibility and complex scale-up/validation processes. Microemulsion technology, as reviewed in this article, promises to resolve many of these challenges. In addition to its development and manufacturing advantages, feasibility to engineer microemulsion formulations by choosing its constituents and nature of formulation vis-à-vis drug candidate demonstrates capability of microemulsion to modulate in-vivo drug release and thereby optimize drug pharmacokinetics and pharmacodynamics. This potential of microemulsion has been used in a few studies to prolong in vivo drug residence time resulting in a more favorable benefit/risk profile for various drugs. Virtues of injectable microemulsion, results related to prolonged-release injectable microemulsion, impact on drug safety and efficacy and possible opportunities have been discussed. A detailed review of research work on microemulsions as well as other parenteral controlled-release formulations was conducted using PubMed, Science Direct and Google Scholar. The fact that microemulsion formulations administered through subcutaneous or intramuscular route would undergo significantly prolonged elimination should be leveraged to develop novel CRI drug products. Such products will find enormous application for several drug candidates which have poor oral pharmacokinetics resulting into poor treatment outcome.

  5. Controlled release of carbofuran from an alginate-bentonite formulation: water release kinetics and soil mobility.

    PubMed

    Fernández-Pérez, M; Villafranca-Sánchez, M; González-Pradas, E; Martinez-López, F; Flores-Céspedes, F

    2000-03-01

    The insecticide-nematicide carbofuran was incorporated in alginate-based granules to obtain controlled-release (CR) properties. The basic formulation [sodium alginate (1.61%)-carbofuran (0. 59%)-water] was modified by addition of sorbents. The effect on carbofuran release rate, caused by the incorporation of natural and acid-treated bentonite (0.5 and 1.0 M H(2)SO(4)) in alginate formulation, was studied by immersion of the granules in water under shaking. The time taken for 50% of the active ingredient to be released into water, t(50), was longer for those formulations containing natural bentonite (6.1 h) or acid-treated bentonite (9.0 and 11.7 h for 0.5 and 1.0 M H(2)SO(4) treatments, respectively) than for the preparation without bentonite (4.7 h). It appears from the results that the release of carbofuran from the various formulations is controlled by a diffusion mechanism according to the n values obtained, which were close to 0.5 in all cases. The mobility of carbofuran from alginate-based CR formulations was investigated by using soil columns packed with a clay soil (53% clay and 0.08% organic matter). Two alginate-based CR formulations containing natural bentonite or acid-treated bentonite (0.5 M H(2)SO(4)) were compared to technical grade carbofuran. The use of alginate-based CR formulations resulted in a reduction of the leached amount of carbofuran compared with the total amount of pesticide leached using the technical product (50 and 75% for CR granules containing natural and acid-treated bentonite, respectively). Alginate-bentonite CR formulations might be efficient systems for reducing carbofuran leaching in clay soils, which would reduce the risk of groundwater pollution.

  6. Controlled release for local delivery of drugs: barriers and models.

    PubMed

    Weiser, Jennifer R; Saltzman, W Mark

    2014-09-28

    Controlled release systems are an effective means for local drug delivery. In local drug delivery, the major goal is to supply therapeutic levels of a drug agent at a physical site in the body for a prolonged period. A second goal is to reduce systemic toxicities, by avoiding the delivery of agents to non-target tissues remote from the site. Understanding the dynamics of drug transport in the vicinity of a local drug delivery device is helpful in achieving both of these goals. Here, we provide an overview of controlled release systems for local delivery and we review mathematical models of drug transport in tissue, which describe the local penetration of drugs into tissue and illustrate the factors - such as diffusion, convection, and elimination - that control drug dispersion and its ultimate fate. This review highlights the important role of controlled release science in development of reliable methods for local delivery, as well as the barriers to accomplishing effective delivery in the brain, blood vessels, mucosal epithelia, and the skin.

  7. Controlled Release System for Localized and Sustained Drug Delivery Applications

    NASA Astrophysics Data System (ADS)

    Rodriguez, Lidia Betsabe

    Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles ( ˜19 mum ) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-coglycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layerswas tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is

  8. Are fluoride releasing dental materials clinically effective on caries control?

    PubMed

    Cury, Jaime Aparecido; de Oliveira, Branca Heloisa; dos Santos, Ana Paula Pires; Tenuta, Livia Maria Andaló

    2016-03-01

    (1) To describe caries lesions development and the role of fluoride in controlling disease progression; (2) to evaluate whether the use of fluoride-releasing pit and fissure sealants, bonding orthodontic agents and restorative materials, in comparison to a non-fluoride releasing material, reduces caries incidence in children or adults, and (3) to discuss how the anti-caries properties of these materials have been evaluated in vitro and in situ. The search was performed on the Cochrane Database of Systematic Reviews and on Medline via Pubmed. Caries is a biofilm-sugar dependent disease and as such it provokes progressive destruction of mineral structure of any dental surface - intact, sealed or restored - where biofilm remains accumulated and is regularly exposed to sugar. The mechanism of action of fluoride released from dental materials on caries is similar to that of fluoride found in dentifrices or other vehicles of fluoride delivery. Fluoride-releasing materials are unable to interfere with the formation of biofilm on dental surfaces adjacent to them or to inhibit acid production by dental biofilms. However, the fluoride released slows down the progression of caries lesions in tooth surfaces adjacent to dental materials. This effect has been clearly shown by in vitro and in situ studies but not in randomized clinical trials. The anti-caries effect of fluoride releasing materials is still not based on clinical evidence, and, in addition, it can be overwhelmed by fluoride delivered from dentifrices. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  9. Controlled exosome release from the retinal pigment epithelium in situ.

    PubMed

    Locke, Christina J; Congrove, Nicole R; Dismuke, W Michael; Bowen, Trent J; Stamer, W Daniel; McKay, Brian S

    2014-12-01

    Retinal Pigment Epithelial cells (RPE) express both GPR143 and myocilin, which interact in a signal transduction-dependent manner. In heterologous systems, activation of GPR143 with ligand causes transient recruitment of myocilin to internalized receptors, which appears to be the entry point of myocilin to the endocytic pathway. In some but not all cells, myocilin also traffics through the multivesicular body (MVB) and is released on the surface of exosomes in a signal transduction-dependent fashion. Little is known regarding the role of exosomes in RPE, but they likely serve as a mode of communication between the RPE and the outer retina. In this study, we used posterior poles with retina removed from fresh human donor eyes as a model to test the relationship between GPR143, myocilin, and exosomes in an endogenous system. We isolated exosomes released by RPE using differential centrifugation of media conditioned by the RPE for 25 min, and then characterized the exosomes using nanoparticle tracking to determine the number and size of the exosomes. Next, we tested whether ligand stimulation of GPR143 using l-DOPA altered RPE exosome release. Finally, we investigated whether myocilin was present on the exosomes released by RPE and whether l-DOPA stimulation of GPR143 caused recruitment of myocilin to the endocytic pathway, as we have previously observed using cultured cells. Activation of GPR143 halted RPE exosome release, while simultaneously recruiting myocilin to the endocytic compartment. Together, our results indicate that GPR143 and myocilin function in a signal transduction system that can control exosome release from RPE.

  10. Biocompatible Collagen Paramagnetic Scaffold for Controlled Drug Release.

    PubMed

    Bettini, Simona; Bonfrate, Valentina; Syrgiannis, Zois; Sannino, Alessandro; Salvatore, Luca; Madaghiele, Marta; Valli, Ludovico; Giancane, Gabriele

    2015-09-14

    A porous collagen-based hydrogel scaffold was prepared in the presence of iron oxide nanoparticles (NPs) and was characterized by means of infrared spectroscopy and scanning electron microscopy. The hybrid scaffold was then loaded with fluorescein sodium salt as a model compound. The release of the hydrosoluble species was triggered and accurately controlled by the application of an external magnetic field, as monitored by fluorescence spectroscopy. The biocompatibility of the proposed matrix was also tested by the MTT assay performed on 3T3 cells. Cell viability was only slightly reduced when the cells were incubated in the presence of the collagen-NP hydrogel, compared to controls. The economicity of the chemical protocol used to obtain the paramagnetic scaffolds as well as their biocompatibility and the safety of the external trigger needed to induce the drug release suggest the proposed collagen paramagnetic matrices for a number of applications including tissue engeneering and drug delivery.

  11. Dendrimeric micelles for controlled drug release and targeted delivery

    PubMed Central

    Ambade, Ashootosh V.; Savariar, Elamprakash N.; Thayumanavan, S.

    2008-01-01

    This review highlights the developments in dendrimer-based micelles for drug delivery. Dendrimers, the perfectly branched monodisperse macromolecules, have certain structural advantages that make them attractive candidates as drug carriers for controlled release or targeted delivery. As polymeric micelle-based approaches precede the work in dendrimers, these are also discussed briefly. The review concludes with a perspective on possible applications of biaryl-based dendrimeric micelles that exhibit environment-dependent conformations, in drug delivery. PMID:16053329

  12. Diisocyanate mediated polyether modified gelatin drug carrier for controlled release

    PubMed Central

    Vijayakumar, Vediappan; Subramanian, Kaliappagounder

    2013-01-01

    Gelatin is an extensively studied biopolymer hydrogel drug carrier due to its biocompatibility, biodegradability and non-toxicity of its biodegraded products formed in vivo. But with the pristine gelatin it is difficult to achieve a controlled and desirable drug release characteristics due to its structural and thermal lability and high solubility in aqueous biofluids. Hence it is necessary to modify its solubility and structural stability in biofluids to achieve controlled release features with improved drug efficacy and broader carrier applications. In the present explorations an effort is made in this direction by cross linking gelatin to different extents using hitherto not studied isocyanate terminated poly(ether) as a macrocrosslinker prepared from poly(ethylene glycol) and isophorone diisocyanate in dimethyl sulfoxide. The crosslinked samples were analyzed for structure by Fourier transform-infrared spectroscopy, thermal behavior through thermogravimetric analysis and differential scanning calorimetry. The cross linked gelatins were biodegradable, insoluble and swellable in biofluids. They were evaluated as a carrier for in vitro drug delivery taking theophylline as a model drug used in asthma therapy. The crosslinking of gelatin decreased the drug release rate by 10–20% depending upon the extent of crosslinking. The modeled drug release characteristics revealed an anomalous transport mechanism. The release rates for ampicillin sodium, 5-fluorouracil and theophylline drugs in a typical crosslinked gelatin carrier were found to depend on the solubility and hydrophobicity of the drugs, and the pH of the fluid. The observed results indicated that this material can prove its mettle as a viable carrier matrix in drug delivery applications. PMID:24493973

  13. Ibuprofen - a Safe Analgesic During Cardiac Surgery Recovery? A Randomized Controlled Trial

    PubMed Central

    Qazi, Saddiq Mohammad; Sindby, Eske Jesper; Nørgaard, Martin Agge

    2015-01-01

    Introduction: Postoperative pain-management with non-steroid anti-inflammatory drugs has been controversial, due to related side-effects. We investigated whether there was a significant difference between an oxycodone-based pain-management regimen versus a slow-release ibuprofen based regimen, in a short term post-cardiac surgery setting. Particular attention was given to the rate of myocardial infarction, sternal healing, gastro-intestinal complications, renal failure and all-cause mortality. Methods: This was a single-centre, open label parallel design randomised controlled study. Patients, who were undergoing cardiac surgery for the first time, were randomly allocated either to a regimen of slow-release oxycodone (10 mg twice daily) or slow-release ibuprofen (800 mg twice daily) combined with lansoprazole. Data relating to blood-tests, angiographies, surgical details and administered medicine were obtained from patient records. The follow-up period was 1 to 37 months (median 25 months). Results: One hundred eighty-two patients were included in the trial and available for intention to treat analysis. There were no significant difference between the groups (P>0.05) in the rates of sternal healing, postoperative myocardial infarction or gastrointestinal bleeding. The preoperative levels of creatinine were found to increase by 100% in nine patients (9.6%) in the ibuprofen group, resulting in an acute renal injury (in accordance with the RIFLE-criteria). Eight of these patients returned to normal renal function within 14 days. The levels of creatinine in patients in the oxycodone group were not found to increase to the same magnitude. Conclusion: The results of this study suggest that patients treated postoperatively, following cardiac surgery, are at no greater risk of harm if short term slow release ibuprofen combined with lansoprazole treatment is used when compared to an oxycodone based regimen. Renal function should, however, be closely monitored and in the

  14. Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report

    PubMed Central

    Ho, Vincent; Stewart, Maxwell; Boyd, Peter

    2008-01-01

    Introduction Oxycodone is a widely-used semisynthetic opioid analgesic that has been used for over eighty years. Oxycodone is known to cause side effects such as nausea, pruritus, dizziness, constipation and somnolence. As far as we are aware cholestatic hepatitis as a result of oxycodone use has not been reported so far in the world literature. Case presentation A 34-year-old male presented with cholestatic jaundice and severe pruritus after receiving oxycodone for analgesia post-T11 vertebrectomy. Extensive laboratory investigations and imaging studies did not reveal any other obvious cause for his jaundice and a liver biopsy confirmed canalicular cholestatis suggestive of drug-induced hepatotoxicity. The patient's symptoms and transaminases normalised on withdrawal of oxycodone confirming that oxycodone was the probable cause of the patient's hepatotoxicity. Conclusion We conclude that cholestatic hepatitis is possibly a rare side effect of oxycodone use. Physicians should be aware of the possibility of this potentially serious picture of drug-induced hepatotoxicity. PMID:18452597

  15. Controlled release matrix tablets of zidovudine: effect of formulation variables on the in vitro drug release kinetics.

    PubMed

    Ravi, Punna Rao; Kotreka, Udaya Kanth; Saha, Ranendra Narayan

    2008-01-01

    The purpose of this research was to design oral controlled release (CR) matrix tablets of zidovudine (AZT) using hydroxypropyl methylcellulose (HPMC), ethyl cellulose (EC) and carbopol-971P (CP) and to study the effect of various formulation factors on in vitro drug release. Release studies were carried out using USP type 1 apparatus in 900 ml of dissolution media. Release kinetics were analyzed using zero-order, Higuchi's square root and Ritger-Peppas' empirical equations. Release rate decreased with increase in polymer proportion and compression force. The release rate was lesser in formulations prepared using CP (20%) as compared to HPMC (20%) as compared to EC (20%). No significant difference was observed in the effect of pH of dissolution media on drug release from formulations prepared using HPMC or EC, but significant difference was observed in CP based formulations. Decrease in agitation speed from 100 to 50 rpm decreased release rate from HPMC and CP formulations but no significant difference was observed in EC formulations. Mechanism of release was found to be dependent predominantly on diffusion of drug through the matrix than polymer relaxation incase of HPMC and EC formulations, while polymer relaxation had a dominating influence on drug release than diffusion incase of CP formulations. Designed CR tablets with pH independent drug release characteristics and an initial release of 17-25% in first hour and extending the release up to 16-20 h, can overcome the disadvantages associated with conventional tablets of AZT.

  16. Nanovalve-Controlled Cargo Release Activated by Plasmonic Heating

    PubMed Central

    Croissant, Jonas; Zink, Jeffrey I.

    2012-01-01

    The synthesis and operation of a light-operated nanovalve that controls the pore openings of mesoporous silica nanoparticles containing gold cores nanoparticles is described. The nanoparticles, consisting of 20 nm gold cores inside ~150 nm mesoporous silica spheres, were synthesized using a unique one-pot method. The nanovalves are comprised of cucurbit[6]uril rings encircling stalks that are attached to the ~2 nm pore openings. Plasmonic heating of the gold core raises the local temperature and decreases the ring-stalk binding constant, thereby unblocking the pore and releasing the cargo molecules that were preloaded inside. Bulk heating of the suspended particles to 60 °C is required to release the cargo, but no bulk temperature change was observed in the plasmonic heating release experiment. High intensity irradiation caused thermal damage to the silica particles, but low intensity illumination caused a sufficient local temperature increase to operate the valves without damaging the nanoparticles containers. These light-stimulated, thermally activated mechanized nanoparticles demonstrate a new system with potential utility for on-command drug release. PMID:22540671

  17. Understanding controlled drug release from mesoporous silicates: theory and experiment.

    PubMed

    Ukmar, T; Maver, U; Planinšek, O; Kaučič, V; Gaberšček, M; Godec, A

    2011-11-07

    Based on the results of carefully designed experiments upgraded with appropriate theoretical modeling, we present clear evidence that the release curves from mesoporous materials are significantly affected by drug-matrix interactions. In experimental curves, these interactions are manifested as a non-convergence at long times and an inverse dependence of release kinetics on pore size. Neither of these phenomena is expected in non-interacting systems. Although both phenomena have, rather sporadically, been observed in previous research, they have not been explained in terms of a general and consistent theoretical model. The concept is demonstrated on a model drug indomethacin embedded into SBA-15 and MCM-41 porous silicates. The experimental release curves agree exceptionally well with theoretical predictions in the case of significant drug-wall attractions. The latter are described using a 2D Fokker-Planck equation. One could say that the interactions affect the relative cross-section of pores where the local flux has a non-vanishing axial component and in turn control the effective transfer of drug into bulk solution. Finally, we identify the critical parameters determining the pore size dependence of release kinetics and construct a dynamic phase diagram of the various resulting transport regimes.

  18. Multimonth controlled small molecule release from biodegradable thin films

    PubMed Central

    Hsu, Bryan B.; Park, Myoung-Hwan; Hagerman, Samantha R.; Hammond, Paula T.

    2014-01-01

    Long-term, localized delivery of small molecules from a biodegradable thin film is challenging owing to their low molecular weight and poor charge density. Accomplishing highly extended controlled release can facilitate high therapeutic levels in specific regions of the body while significantly reducing the toxicity to vital organs typically caused by systemic administration and decreasing the need for medical intervention because of its long-lasting release. Also important is the ability to achieve high drug loadings in thin film coatings to allow incorporation of significant drug amounts on implant surfaces. Here we report a sustained release formulation for small molecules based on a soluble charged polymer–drug conjugate that is immobilized into nanoscale, conformal, layer-by-layer assembled films applicable to a variety of substrate surfaces. We measured a highly predictable sustained drug release from a polymer thin film coating of 0.5–2.7 μm that continued for more than 14 mo with physiologically relevant drug concentrations, providing an important drug delivery advance. We demonstrated this effect with a potent small molecule nonsteroidal anti-inflammatory drug, diclofenac, because this drug can be used to address chronic pain, osteoarthritis, and a range of other critical medical issues. PMID:25092310

  19. Osmotic, controlled-release methylphenidate for the treatment of ADHD.

    PubMed

    Coghill, David; Seth, Sarah

    2006-10-01

    Methylphenidate (MPH) is the most commonly used and best-studied stimulant medication for attention-deficit hyperactivity disorder. However, its short duration of action usually results in a requirement to administer multiple daily doses in order to achieve optimal clinical benefit. Although a wax-matrix-based SR formulation of MPH has been available since the 1990s, it was not well accepted into clinical practice. The variable absorption profile and lack of an immediate-release component results in a slower onset of action compared with immediate-release MPH. Hence, there was a need to develop alternative longer-lasting preparations of MPH that were as efficacious as IR MPH, but which also addressed the problems inherent in multiple daily dosing. An osmotic, controlled-release (OROS) formulation of MPH HCl has been developed over the past 10 years for once-daily administration. OROS MPH has been widely accepted by clinicians and is now the most widely prescribed MPH product in North America. Clinical trials have shown OROS MPH to have a continued action over a 12-h period, to be superior to placebo and to be as effective as immediate-release MPH dosed three times daily, in reducing symptoms of attention-deficit hyperactivity disorder, with similar incidence of side effects. There have been a smaller number of trials comparing OROS MPH with non-stimulant treatments, such as atomoxetine.

  20. Oxytrex: an oxycodone and ultra-low-dose naltrexone formulation.

    PubMed

    Webster, Lynn R

    2007-08-01

    Oxytrex (Pain Therapeutics, Inc.) is an oral opioid that combines a therapeutic amount of oxycodone with an ultra-low dose of the antagonist naltrexone. Animal data indicate that this combination minimizes the development of physical dependence and analgesic tolerance while prolonging analgesia. Oxytrex is in late-stage clinical development by Pain Therapeutics for the treatment of moderate-to-severe chronic pain. To evaluate the safety and efficacy of the oxycodone/naltrexone combination, three clinical studies have been conducted, one in healthy volunteers and the other two in patients with chronic pain. The putative mechanism of ultra-low-dose naltrexone is to prevent an alteration in G-protein coupling by opioid receptors that is associated with opioid tolerance and dependence. Opioid agonists are initially inhibitory but become excitatory through constant opioid receptor activity. The agonist/antagonist combination of Oxytrex may reduce the conversion from an inhibitory to an excitatory receptor, thereby decreasing the development of tolerance and physical dependence.

  1. Controlled release of ibuprofen by meso-macroporous silica

    NASA Astrophysics Data System (ADS)

    Santamaría, E.; Maestro, A.; Porras, M.; Gutiérrez, J. M.; González, C.

    2014-02-01

    Structured meso-macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (EO19PO39EO19) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption-desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso-macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system.

  2. Development of controlled drug release systems based on thiolated polymers.

    PubMed

    Bernkop-Schnürch, A; Scholler, S; Biebel, R G

    2000-05-03

    The purpose of the present study was to generate mucoadhesive matrix-tablets based on thiolated polymers. Mediated by a carbodiimide, L-cysteine was thereby covalently linked to polycarbophil (PCP) and sodium carboxymethylcellulose (CMC). The resulting thiolated polymers displayed 100+/-8 and 1280+/-84 micromol thiol groups per gram, respectively (means+/-S.D.; n=6-8). In aqueous solutions these modified polymers were capable of forming inter- and/or intramolecular disulfide bonds. The velocity of this process augmented with increase of the polymer- and decrease of the proton-concentration. The oxidation proceeded more rapidly within thiolated PCP than within thiolated CMC. Due to the formation of disulfide bonds within thiol-containing polymers, the stability of matrix-tablets based on such polymers could be strongly improved. Whereas tablets based on the corresponding unmodified polymer disintegrated within 2 h, the swollen carrier matrix of thiolated CMC and PCP remained stable for 6.2 h (mean, n=4) and more than 48 h, respectively. Release studies of the model drug rifampicin demonstrated that a controlled release can be provided by thiolated polymer tablets. The combination of high stability, controlled drug release and mucoadhesive properties renders matrix-tablets based on thiolated polymers useful as novel drug delivery systems.

  3. Novel thermogelling dispersions of polymer nanoparticles for controlled protein release.

    PubMed

    Cai, Tong; Hu, Peter D; Sun, Manwu; Zhou, Jun; Tsai, Yi-Ting; Baker, David; Tang, Liping

    2012-11-01

    A novel poly(oligo(ethylene glycol) methyl ether methacrylate-co-oligo(ethylene glycol) ethyl ether methacrylate)-poly(acrylic acid) interpenetrating network (IPN) nanoparticle was synthesized. The temperature-responsive properties of the IPN nanoparticles were investigated by a dynamic light scattering method. Atomic force microscopic images confirmed the homogenous and monodisperse morphology of the IPN nanoparticles. Both visual observation and viscosity testing demonstrated that the IPN nanoparticles exhibit thermogelling properties at body temperature, 37 °C. Subsequent studies verified that such temperature-sensitive properties of IPN nanoparticles allow their ease of injection and then slow release of model proteins, both in vitro and in vivo. Histological analysis showed that our IPN implants exerted minimal inflammation following subcutaneous implantation. Our results support the idea that, by simply mixing with proteins of interest, the novel IPN nanoparticles can be used to form in situ thermogelling devices for controlled protein release. This paper discusses a temperature responsive interpenetrating network (IPN) polymeric nanoparticle that can be used to form in situ thermogelling devices for controlled protein release by simply mixing them with proteins of interest. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Problems with the use of oxycodone compound in patients with chronic pain.

    PubMed

    Maruta, T; Swanson, D W

    1981-12-01

    In a pain management program (200 patients), a group of daily users of oxycodone compound (29 patients) and a subgroup who were taking a "high dose" of oxycodone compound (13 patients) were compared with a group of 171 non-users of oxycodone compound. A significantly lower treatment success rate was observed in the users (P = 0.04) and high-dose users (P = 0.03). A similar trend was seen in preliminary data available in a larger sample (514 patients). Continued study of these findings is necessary. Meanwhile, in patients with chronic pain, there should be cautious use of this compound.

  5. Budget impact analysis of tapentadol extended release for the treatment of moderate to severe chronic noncancer pain.

    PubMed

    Merchant, Sanjay; Noe, Les L; Howe, Andrew; Duff, Steve; Gricar, Joe; Ogden, Kristine; Mody, Samir H

    2013-05-01

    Opioids are commonly used to manage chronic pain. Although traditional μ-opioids are effective in reducing pain, they are often associated with opioid-induced side effects (OISEs) that can limit treatment effectiveness. Studies have shown that tapentadol extended release (ER) has a lower incidence of gastrointestinal adverse events than oxycodone controlled release (CR) at equianalgesic doses. A model was developed to estimate the budget impact of placing tapentadol ER on a hypothetical US health plan formulary of Schedule II long-acting opioids. We estimated annual direct health care costs for patients who received 6-month therapy with long-acting formulations of tapentadol, oxycodone, morphine, hydromorphone, oxymorphone, or fentanyl. Costs included medications, copayments, OISE management, and switching/discontinuation. Published estimates of incidence/prevalence, OISEs, and pain management resources and costs were used. The base case analysis assumed a 10% formulary share of tapentadol ER with a 10% decrease of oxycodone CR. The resulting per-member per-month (PMPM) formulary cost differences and results of a 1-way sensitivity analysis are reported. In a health plan of 500,000 members, 2600 (0.52%) are estimated to experience chronic pain annually. Adding tapentadol ER to the formulary was associated with an annual budget savings of $148,945 ($0.0248 PMPM). This savings was achieved through a decrease in both pharmacy costs ($144,062; $0.0240 PMPM) and medical costs ($4883; $0.0008 PMPM). Cost decreases were driven by lower daily average consumption and fewer OISEs with tapentadol ER versus oxycodone CR, leading to reduced resource utilization over 6 months of treatment. Sensitivity analyses showed results were most sensitive to drug acquisition costs. Our results suggest that replacing 10% of oxycodone CR's formulary share with tapentadol ER would decrease the overall budget of a health plan with 500,000 members. Placing tapentadol ER on a health plan

  6. Short-term oxycodone treatment does not affect electrogenic ion transport in isolated mucosa from the human rectosigmoid colon.

    PubMed

    Nilsson, Matias; Brock, Christina; Poulsen, Jakob Lykke; Bindslev, Niels; Hansen, Mark Berner; Louring Christrup, Lona; Drewes, A M

    2016-01-01

    Opioid therapy is associated with altered secretion and motility of the gut. The relative contribution of decreased secretion to the development of opioid-induced constipation remains unknown. Twenty-five healthy males were treated with oxycodone for 5 d in a placebo-controlled, randomised cross-over design. Gastrointestinal adverse effects were assessed with validated questionnaires (bowel function index and gastrointestinal symptom rating scale). Rectosigmoid mucosal biopsies were taken at baseline and on day 5 during both treatments and mounted in Ussing chambers. Electrogenic ion transport parameters (short circuit current (SCC) and slope conductance) were measured after addition of secretagogues (prostaglandin E2 (PGE2) (6 μm), theophylline (400 μm)), and an inhibitor (ouabain (200 μm)). Additionally, morphine (50 μm) was added to investigate the direct opioid effect on colonic mucosa. Questionnaires showed pronounced bowel symptoms, including constipation during oxycodone treatment (eight-fold increase in bowel function index score from day 1 to day 5 (p < 0.001) while no significant change occurred during placebo treatment (p = 0.47). Basal SCC and slope conductance did not differ between treatments (all p > 0.05) and application with PGE2, theophylline, and ouabain yielded comparable results on all examinations (all p > 0.05). Morphine application consistently did not evoke a change in ion transport. Compared to placebo, epithelial electrogenic ion transport is not altered in mucosal biopsies from the rectosigmoid colon following 5-d oxycodone treatment. The secretory mechanisms in isolated mucosa appear to play a negligible role in the development of opioid-induced constipation.

  7. Lycopene/arabinoxylan gels: rheological and controlled release characteristics.

    PubMed

    Hernández-Espinoza, Ana B; Piñón-Muñiz, Marina I; Rascón-Chu, Agustín; Santana-Rodríguez, Víctor M; Carvajal-Millan, Elizabeth

    2012-02-28

    Arabinoxylan gels exhibiting different rheological and lycopene transport properties were obtained by modifying the polysaccharide concentration from 3 to 4% (w/v). The apparent lycopene diffusion coefficient decreased from 2.7 × 10⁻⁷ to 2.4 × 10⁻⁷ cm²/s as the arabinoxylan concentration in the gel changed from 3 to 4% (w/v). A low amount of lycopene is released by diffusion from arabinoxylan gels. These results indicate that arabinoxylan gels could be carriers for lycopene delivery in specific sites after network degradation. The possibility to modulate lycopene release from arabinoxylan gels makes these biomaterials potential candidates for the controlled delivery of biomolecules.

  8. Novel Thermogelling Dispersions of Polymer Nanoparticles for Controlled Protein Release

    PubMed Central

    Cai, Tong; Hu, Peter D.; Sun, Manwu; Zhou, Jun; Tsai, Yi-Ting; Baker, David; Tang, Liping

    2012-01-01

    A novel poly(oligo(ethylene glycol) methyl ether methacrylate-co-oligo(ethylene glycol) ethyl ether methacrylate)/ poly(acrylic acid) interpenetrating network (IPN) nanoparticle was synthesized. The temperature-responsive properties of the IPN nanoparticles were investigated by dynamic light scattering method. Atomic force microscopic images confirm the homogenous and mono-disperse morphology of the IPN nanoparticles. Both visual observation and viscosity testing demonstrated that the IPN nanoparticles exhibit thermogelling properties at body temperature, 37°C. Subsequent studies verified that such temperature sensitive properties of IPN nanoparticles allow their ease of injection and then slow release of model proteins, both in vitro and in vivo. Histological analysis showed that our IPN implants exerted minimal inflammation following subcutaneous implantation. Our results support that, by simply mixing with proteins of interest, the novel IPN nanoparticles can be used to form in situ thermogelling devices for controlled protein release. PMID:22349097

  9. Optical control of insulin release using a photoswitchable sulfonylurea

    PubMed Central

    Broichhagen, Johannes; Schönberger, Matthias; Cork, Simon C.; Frank, James A.; Marchetti, Piero; Bugliani, Marco; Shapiro, A. M. James; Trapp, Stefan; Rutter, Guy A.; Hodson, David J.; Trauner, Dirk

    2014-01-01

    Sulfonylureas are widely prescribed for the treatment of type 2 diabetes mellitus (T2DM). Through their actions on ATP-sensitive potassium (KATP) channels, sulfonylureas boost insulin release from the pancreatic beta cell mass to restore glucose homeostasis. A limitation of these compounds is the elevated risk of developing hypoglycemia and cardiovascular disease, both potentially fatal complications. Here, we describe the design and development of a photoswitchable sulfonylurea, JB253, which reversibly and repeatedly blocks KATP channel activity following exposure to violet-blue light. Using in situ imaging and hormone assays, we further show that JB253 bestows light sensitivity upon rodent and human pancreatic beta cell function. Thus, JB253 enables the optical control of insulin release and may offer a valuable research tool for the interrogation of KATP channel function in health and T2DM. PMID:25311795

  10. Optical control of insulin release using a photoswitchable sulfonylurea.

    PubMed

    Broichhagen, Johannes; Schönberger, Matthias; Cork, Simon C; Frank, James A; Marchetti, Piero; Bugliani, Marco; Shapiro, A M James; Trapp, Stefan; Rutter, Guy A; Hodson, David J; Trauner, Dirk

    2014-10-14

    Sulfonylureas are widely prescribed for the treatment of type 2 diabetes mellitus (T2DM). Through their actions on ATP-sensitive potassium (KATP) channels, sulfonylureas boost insulin release from the pancreatic beta cell mass to restore glucose homeostasis. A limitation of these compounds is the elevated risk of developing hypoglycemia and cardiovascular disease, both potentially fatal complications. Here, we describe the design and development of a photoswitchable sulfonylurea, JB253, which reversibly and repeatedly blocks KATP channel activity following exposure to violet-blue light. Using in situ imaging and hormone assays, we further show that JB253 bestows light sensitivity upon rodent and human pancreatic beta cell function. Thus, JB253 enables the optical control of insulin release and may offer a valuable research tool for the interrogation of KATP channel function in health and T2DM.

  11. Graphene as a photothermal switch for controlled drug release

    NASA Astrophysics Data System (ADS)

    Matteini, Paolo; Tatini, Francesca; Cavigli, Lucia; Ottaviano, Stefania; Ghini, Giacomo; Pini, Roberto

    2014-06-01

    Graphene has recently emerged as a novel material in the biomedical field owing to its optical properties, biocompatibility, large specific surface area and low cost. In this paper, we provide the first demonstration of the possibility of using light to remotely trigger the release of drugs from graphene in a highly controlled manner. Different drugs including chemotherapeutics and proteins are firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a biopolymer film and then released by individual millisecond-long light pulses generated by a near infrared (NIR) laser. Here graphene plays the dual role of a versatile substrate for temporary storage of drugs and an effective transducer of NIR-light into heat. Drug release appears to be narrowly confined within the size of the laser spot under noninvasive conditions and can be precisely dosed depending on the number of pulses. The approach proposed paves the way for tailor-made pharmacological treatments of chronic diseases, including cancer, anaemia and diabetes.Graphene has recently emerged as a novel material in the biomedical field owing to its optical properties, biocompatibility, large specific surface area and low cost. In this paper, we provide the first demonstration of the possibility of using light to remotely trigger the release of drugs from graphene in a highly controlled manner. Different drugs including chemotherapeutics and proteins are firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a biopolymer film and then released by individual millisecond-long light pulses generated by a near infrared (NIR) laser. Here graphene plays the dual role of a versatile substrate for temporary storage of drugs and an effective transducer of NIR-light into heat. Drug release appears to be narrowly confined within the size of the laser spot under noninvasive conditions and can be precisely dosed depending on the number of pulses. The approach proposed paves the way for tailor

  12. Controlled release of ibuprofen by meso–macroporous silica

    SciTech Connect

    Santamaría, E. Maestro, A.; Porras, M.; Gutiérrez, J.M.; González, C.

    2014-02-15

    Structured meso–macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO{sub 19}PO{sub 39}EO{sub 19}) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption–desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso–macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system. - Graphical abstract: Ibuprofen release profiles for the materials obtained from samples P84{sub m}eso (black diamonds), P84{sub 2}0% (white squares), P84{sub 5

  13. Thermal post-treatment alters nutrient release from a controlled-release fertilizer coated with a waterborne polymer.

    PubMed

    Zhou, Zijun; Du, Changwen; Li, Ting; Shen, Yazhen; Zhou, Jianmin

    2015-09-08

    Controlled-release fertilizers (CRF) use a controlled-release technology to enhance the nutrient use efficiency of crops. Many factors affect the release of nutrients from the waterborne polymer-coated CRF, but the effects of thermal post-treatments remain unclear. In this study, a waterborne polyacrylate-coated CRF was post-treated at different temperatures (30 °C, 60 °C, and 80 °C) and durations (2, 4, 8, 12, and 24 h) after being developed in the Wurster fluidized bed. To characterize the polyacrylate membrane, and hence to analyze the mechanism of nutrient release, Fourier transform mid-infrared spectroscopy, scanning electron microscopy, and atomic force microscopy were employed. The nutrient-release model of CRF post-treated at 30 °C was the inverse "L" curve, but an increased duration of the post-treatment had no effect. The nutrient-release model was "S" curve and nutrient-release period was enhanced at higher post-treatment temperatures, and increased post-treatment duration lengthened slowed nutrient release due to a more compact membrane and a smoother membrane surface as well as a promoted crosslinking action. CRF equipped with specified nutrient-release behaviors can be achieved by optimizing the thermal post-treatment parameters, which can contribute to the development and application of waterborne polymer-coated CRF and controlled-release technologies.

  14. Thermal post-treatment alters nutrient release from a controlled-release fertilizer coated with a waterborne polymer

    NASA Astrophysics Data System (ADS)

    Zhou, Zijun; Du, Changwen; Li, Ting; Shen, Yazhen; Zhou, Jianmin

    2015-09-01

    Controlled-release fertilizers (CRF) use a controlled-release technology to enhance the nutrient use efficiency of crops. Many factors affect the release of nutrients from the waterborne polymer-coated CRF, but the effects of thermal post-treatments remain unclear. In this study, a waterborne polyacrylate-coated CRF was post-treated at different temperatures (30 °C, 60 °C, and 80 °C) and durations (2, 4, 8, 12, and 24 h) after being developed in the Wurster fluidized bed. To characterize the polyacrylate membrane, and hence to analyze the mechanism of nutrient release, Fourier transform mid-infrared spectroscopy, scanning electron microscopy, and atomic force microscopy were employed. The nutrient-release model of CRF post-treated at 30 °C was the inverse “L” curve, but an increased duration of the post-treatment had no effect. The nutrient-release model was “S” curve and nutrient-release period was enhanced at higher post-treatment temperatures, and increased post-treatment duration lengthened slowed nutrient release due to a more compact membrane and a smoother membrane surface as well as a promoted crosslinking action. CRF equipped with specified nutrient-release behaviors can be achieved by optimizing the thermal post-treatment parameters, which can contribute to the development and application of waterborne polymer-coated CRF and controlled-release technologies.

  15. Thermal post-treatment alters nutrient release from a controlled-release fertilizer coated with a waterborne polymer

    PubMed Central

    Zhou, Zijun; Du, Changwen; Li, Ting; Shen, Yazhen; Zhou, Jianmin

    2015-01-01

    Controlled-release fertilizers (CRF) use a controlled-release technology to enhance the nutrient use efficiency of crops. Many factors affect the release of nutrients from the waterborne polymer-coated CRF, but the effects of thermal post-treatments remain unclear. In this study, a waterborne polyacrylate-coated CRF was post-treated at different temperatures (30 °C, 60 °C, and 80 °C) and durations (2, 4, 8, 12, and 24 h) after being developed in the Wurster fluidized bed. To characterize the polyacrylate membrane, and hence to analyze the mechanism of nutrient release, Fourier transform mid-infrared spectroscopy, scanning electron microscopy, and atomic force microscopy were employed. The nutrient-release model of CRF post-treated at 30 °C was the inverse “L” curve, but an increased duration of the post-treatment had no effect. The nutrient-release model was “S” curve and nutrient-release period was enhanced at higher post-treatment temperatures, and increased post-treatment duration lengthened slowed nutrient release due to a more compact membrane and a smoother membrane surface as well as a promoted crosslinking action. CRF equipped with specified nutrient-release behaviors can be achieved by optimizing the thermal post-treatment parameters, which can contribute to the development and application of waterborne polymer-coated CRF and controlled-release technologies. PMID:26348791

  16. Controlled release experiments with nonylphenol in aquatic microcosms.

    PubMed

    Pfister, Gerd; Jüttner, Ingrid; Severin, Gabriele F; Schramm, Karl-Werner; Kettrup, Antonius

    2003-01-01

    A method of controlled release of technical nonylphenol (tNP) was developed to simulate realistic exposure in ecotoxicological studies on aquatic organisms. The direct addition of tNP from an aqueous stock solution into 50 ml of water led to a concentration decrease of 80 to 90% weight/volume (w/v) from nominal values within 48 h. The inclusion of tNP in semipermeable low-density polyethylene (LDPE) lay-flat tubing (controlled-release devices [CRDs]) of different length allowed a continuous release into pure water at a rate of about 30 microg/cm2/d. Using CRDs in aquaria containing 15 L of 63-microm-filtered lake water, eight different concentrations with maxima between 38.1 and 326.7 microg/L were maintained for 11 d. During a second experiment in 15-L aquaria, five replicates of three concentrations were maintained using CRDs of the same length. Concentrations after 38 d varied between 0.1 and 6.7, 26.1 and 41.9, and 49.9 and 76.0 microg/L. In aquatic microcosms containing 230 L of lake water, a natural plankton community, 50 L of sediment, and macrophytes, seven different tNP concentrations (maxima 11-120.1 microg/L) were maintained over 45 d using CRDs of different length. They were replaced after 14 and 25 d because release of tNP was slower than predicted from laboratory experiments. Concentrations in the top 1-cm sediment layer were on average 19 times higher during the dosing period than concentrations in the water at the same time. In the sediments, different levels of applications led to concentrations that differed less distinctly than in the water. This method is suitable for exposing aquatic organisms continuously to constant, ecologically relevant concentrations of NP and represents an improvement over previous dosing methods in which exposure varied.

  17. Controlled release of plasmid DNA from hyaluronan nanoparticles.

    PubMed

    Mahor, Sunil; Collin, Estelle; Dash, Biraja C; Pandit, Abhay

    2011-07-01

    Encapsulation of plasmid DNA (pDNA) in nanoparticulate gene delivery systems offers the possibility of control in dosing, enhanced pDNA uptake, increased resistance to nuclease degradation and sustained release of functionally active pDNA over time. Extracellular matrix based biomaterial i.e. hyaluronan (HA) was used to encapsulate pDNA (pCMV-GLuc, Gaussia Luciferase reporter plasmid DNA having CMV promoter) in submicron size particulate system. Nano size range (~400-600 nm) pDNA loaded hyaluronan nanoparticles were formulated by ionic gelation followed by the cross-linking method with high encapsulation efficiency (~75-85%). The particle preparation process was further optimized for molecular weight, cross-linking method, cross-linking time and plasmid/polymer ratio. The entrapped plasmid maintained its structural and functional integrity as revealed by agarose gel electrophoresis. The pDNA was released from the hyaluronan nanoparticles in a controlled manner over a period of one month. In vitro transfection by one-week released pDNA from nanoparticles with transfecting agent branched polyethyleneimine (bPEI) resulted in significantly higher expression levels than those in pDNA alone which demonstrated the functional bioactivity of released pDNA. For cellular localization studies, the hyaluronan nanoparticles encapsulated with FITC-dextran were incubated with adipose derived stem cells (ADSCs) and localization in the cellular environment were investigated. The results of this study illustrate that hyaluronan nanoparticles were rapidly internalized by the cells through nonspecific endocytosis and remained intact in the cytosol for up to 24 h.

  18. A microfluidic chip for controlled release of drugs from microcapsules

    PubMed Central

    Cheng, Wen-Chuan; He, Yuan; Chang, An-Yi; Que, Long

    2013-01-01

    A new microfluidic device with liquid-droplet merging and droplet storage functions for the controlled release of drugs from microcapsules is reported. A switching channel is designed and integrated within the microfluidic device, facilitating the generation and capturing of uniform droplets by the storage chambers. The drug model is the MnCO3 microparticle, which is encapsulated by a microcapsule and fabricated using a simple layer-by-layer nanoassembly process. The merging function is used for dynamically adding the control solution into the droplets, which contain drugs within the microcapsules (DWμCs) and water. The storage chambers are used for collecting DWμCs-laden droplets so that the controlled-drug release in specific droplets can be monitored for an extended period of time, which has been experimentally implemented successfully. This technology could offer a promising technical platform for the long-term observation and studies of drug effects on specific cells in a controlled manner, which is especially useful for single cell analysis. PMID:24396536

  19. INVITED PAPER: Control of sudden releases in channel flow

    NASA Astrophysics Data System (ADS)

    Katopodes, Nikolaos D.

    2009-12-01

    We present a method for the detection and real-time control of chemical releases in channel flow. Sensor arrays capable of detecting a broad menu of chemical agents are required at strategic locations of the channel. The sensors detect the instantaneous, spatially distributed concentration of the chemical agent and transmit the associated information to a predictive control model. The model provides optimal operation scenarios for computer controlled bleed valves mounted on the channel walls and connected to a common manifold. Control and elimination of the chemical cloud are achieved by optimal blowing and suction of ambient fluid. Gradient information is obtained by use of adjoint equations, so optimization of the control actions is achieved with the highest possible efficiency. The control is optimized over a finite prediction horizon and instructions are sent to the valve manifold. Next, the sensor arrays detect all changes effected by the control and report them to the control model, which advances the process over the next control horizon. Non-reflective boundary conditions for the adjoint equations are derived by a characteristic analysis, which minimizes spurious information in the computation of sensitivities.

  20. Voltage-Responsive Controlled Release Film with Cargo Release Self-Monitoring Property Based on Hydrophobicity Switching.

    PubMed

    Jiao, Xiangyu; Li, Yanan; Li, Fengyu; Sun, Ruijuan; Wang, Wenqian; Wen, Yongqiang; Song, Yanlin; Zhang, Xueji

    2017-03-16

    Herein, voltage-responsive controlled release film was constructed by grafting ferrocene on the mesoporous inverse opal photonic crystal (mIOPC). The film achieved free-blockage controlled release and realized the monitoring of cargo release without external indicator. Free-blockage was attributed to the voltage switchable nanovalves which undergo hydrophobic-to-hydrophilic transition when applying voltage. Monitoring of cargo release was attributed to the optical property of mIOPC, the bandgap of mIOPC had a red shift when the solution invaded in. The film was hydrophobic enough to stop solution intrusion. Once the voltage was applied, the film became hydrophilic, leading to invasion of the solution. As a result, the cargos were released and the bandgap of mIOPC was red-shifted. Therefore, in this paper both a free-blockage controlled release film and a release sensing system was prepared. The study provides new insights into highly effective controlled release and release sensing without indicator.

  1. A mathematical model for pulsatile release: controlled release of rhodamine B from UV-crosslinked thermoresponsive thin films.

    PubMed

    Yang, Rongbing; Vo T N, Tuoi; Gorelov, Alexander V; Aldabbagh, Fawaz; Carroll, William M; Meere, Martin G; Rochev, Yury

    2012-05-10

    A controlled drug delivery system fabricated from a thermoresponsive polymer was designed to obtain a pulsatile release profile which was triggered by altering the temperature of the dissolution medium. Two stages of release behaviour were found: fast release for a swollen state and slow (yet significant and non-negligible) release for a collapsed state. Six cycles of pulsatile release between 4 °C and 40 °C were obtained. The dosage of drug (rhodamine B) released in these cycles could be controlled to deliver approximately equal doses by altering the release time in the swollen state. However, for the first cycle, the swollen release rate was found to be large, and the release time could not be made short enough to prevent a larger dose than desired being delivered. A model was developed based on Fick's law which describes pulsatile release mathematically for the first time, and diffusion coefficients at different temperatures (including temperatures corresponding to both the fully swollen and collapsed states) were estimated by fitting the experimental data with the theoretical release profile given by this model. The effect of temperature on the diffusion coefficient was studied and it was found that in the range of the lower critical solution temperature (LCST), the diffusion coefficient increased with decreasing temperature. The model predicts that the effective lifetime of the system lies in the approximate range of 1-42 h (95% of drug released), depending on how long the system was kept at low temperature (below the LCST). Therefore this system can be used to obtain a controllable pulsatile release profile for small molecule drugs thereby enabling optimum therapeutic effects.

  2. Nanostructured aligned CNT platforms enhance the controlled release of a neurotrophic protein from polypyrrole.

    PubMed

    Thompson, Brianna C; Chen, Jun; Moulton, Simon E; Wallace, Gordon G

    2010-04-01

    An aligned CNT array membrane electrode has been used as a nanostructured supporting platform for polypyrrole (PPy) films, exhibiting significant improvement in the controlled release of neurotrophin. In terms of linearity of release, stimulated to unstimulated control of NT-3 release and increased mass and % release of incorporated NT-3, the nanostructured material performed more favourably than the flat PPy film.

  3. Nanostructured aligned CNT platforms enhance the controlled release of a neurotrophic protein from polypyrrole

    NASA Astrophysics Data System (ADS)

    Thompson, Brianna C.; Chen, Jun; Moulton, Simon E.; Wallace, Gordon G.

    2010-04-01

    An aligned CNT array membrane electrode has been used as a nanostructured supporting platform for polypyrrole (PPy) films, exhibiting significant improvement in the controlled release of neurotrophin. In terms of linearity of release, stimulated to unstimulated control of NT-3 release and increased mass and % release of incorporated NT-3, the nanostructured material performed more favourably than the flat PPy film.

  4. Photosensitive cross-linked block copolymers with controllable release.

    PubMed

    Yu, Lili; Lv, Cong; Wu, LiZhu; Tung, ChenHo; Lv, WanLiang; Li, ZhongJin; Tang, XinJing

    2011-01-01

    We intend to form photosensitive block copolymer micelles for controllable release of encapsulated substances. Here, we designed and synthesized a new photocleavable cross-linker (2-nitrophenyl ethylene glycol dimethacrylate) for methyl methacrylate (MMA) atom transfer radical polymerization. Four different ratios (0:1, 1:26, 1:16, 1:8.8) of the photocleavable cross-linker to MMA monomer were used and four block copolymers (P0, P1, P2, P3) were synthesized with PEO-Br as the macroinitiator. Gel permeation chromatography and (1) H NMR studies showed that linear polymer molecules could be cross-linked by the photocleavable linker. The fluorescence studies of the encapsulated Nile Red (NR) showed that there were lower critical micelle concentrations for the polymer P1, P2 and P3 than polymer P0. And dynamic light scattering and SEM confirmed the formation of polymer micelles. Photolysis experiments demonstrated that NR encapsulated in the polymer micelles could be released upon UV irradiation (365 nm, 11 mW cm(-2)) due to the breakage of the photocleavable linker and the generation of more hydrophilic acid moieties, which destabilized polymer micelles. Our study shows a new strategy for the possibility of photocontrollable drug release for hydrophobic drugs.

  5. Cationic liposomes in double emulsions for controlled release.

    PubMed

    Wang, Qing; Rojas, Edith C; Papadopoulos, Kyriakos D

    2012-10-01

    Liposomes containing a model active component were entrapped within the internal aqueous phase (W(1)) of W(1)/O/W(2) double emulsions, thus providing a double-encapsulation system. Our motivation for the development of this system is to prevent liposomes from interacting with unfavorable physicochemical conditions and to optimize this system for dermal vaccine delivery. The choice of cationic liposomes is based on the fact that they have high penetration ability across the skin and hair follicles, and an adjuvant effect on the activation of antigen-presenting cells. Cryo-SEM images showed that liposomes are well encapsulated within the W(1) phase, indicating that most liposomes remain intact during the homogenization step of formulation fabrication. Freezing the n-hexadecane oil (O) phase of the double-encapsulation formulations preserved their stability during the storage, and subsequent oil-thawing induced progressive release of liposomes and their contents. The release mechanism upon the freeze-thaw treatment was internal coalescence followed by external coalescence. Our results also indicated that tuning the concentration of L-α-phosphatidylcholine (PC) lipid in the cationic liposomes can control the release rate from the double-encapsulation formulations. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Dexamethasone electrically controlled release from polypyrrole-coated nanostructured electrodes.

    PubMed

    Leprince, Lucas; Dogimont, Audrey; Magnin, Delphine; Demoustier-Champagne, Sophie

    2010-03-01

    One of the key challenges to engineering neural interfaces is to reduce their immune response toward implanted electrodes. One potential approach to minimize or eliminate this undesired early inflammatory tissue reaction and to maintain signal transmission quality over time is the delivery of anti-inflammatory biomolecules in the vicinity of the implant. Here, we report on a facile and reproducible method for the fabrication of high surface area nanostructured electrodes coated with an electroactive polymer, polypyrrole (PPy) that can be used to precisely release drug by applying an electrical stimuli. The method consists of the electropolymerization of PPy incorporated with drug, dexamethasone (DEX), onto a brush of metallic nanopillars, obtained by electrodeposition of the metal within the nanopores of gold-coated polycarbonate template. The study of the release of DEX triggered by electrochemical stimuli indicates that the system is a true electrically controlled release system. Moreover, it appears that the presence of metallic nanowires onto the electrode surface improves the adherence between the polymer and the electrode and increases the electroactivity of the PPy coating.

  7. Lipolysis and structure controlled drug release from reversed hexagonal mesophase.

    PubMed

    Garti, Nissim; Hoshen, Geut; Aserin, Abraham

    2012-06-01

    The present work investigates a system composed of a ternary reversed hexagonal mesophase (H(II)) loaded with a lipase for modulating drug delivery capabilities of the system. Thermomyces lanuginosa lipase was solubilized into H(II) mesophase for the benefits of continuing lipolysis of the lipids, consequently disordering and decomposing the hexagonal mesophase and thereby enhancing the diffusion of the encapsulated drug. A single transition from the H(II) structure to a random micellar phase was detected during the lipolysis. In the first lipolysis stage the hexagonal system (glycerol monooleate, tricaprylin, and water) preserved its symmetry within ca. 200 min. During this step about 40-60% molar of the lipids were hydrolyzed, and a gradual shrinking of the H(II) cylinders (decrease of 8 Å in lattice parameter) was detected. In the second lipolysis stage, the H(II) mesophase gradually disintegrated (faster rate) and the release of a model drug (sodium diclofenac) was significantly enhanced, which was assumed to be lipolysis rate-controlled. After about 15 h the H(II) mesophase was disintegrated into two dispersed immiscible phases. The release obeyed two-step Higuchi kinetics with two consecutive linear correlations of the drug release. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Tunable controlled release of molecular species from Halloysite nanotubes

    NASA Astrophysics Data System (ADS)

    Elumalai, Divya Narayan

    Encouraged by potential applications in rust coatings, self-healing composites, selective delivery of drugs, and catalysis, the transport of molecular species through Halloysite nanotubes (HNTs), specifically the storage and controlled release of these molecules, has attracted strong interest in recent years. HNTs are a naturally occurring biocompatible nanomaterial that are abundantly and readily available. They are alumosilicate based tubular clay nanotubes with an inner lumen of 15 nm and a length of 600-900 nm. The size of the inner lumen of HNTs may be adjusted by etching. The lumen can be loaded with functional agents like antioxidants, anticorrosion agents, flame-retardant agents, drugs, or proteins, allowing for a sustained release of these agents for hours. The release times can be further tuned for days and months by the addition of tube end-stoppers. In this work a three-dimensional, time-quantified Monte Carlo model that efficiently describes diffusion through and from nanotubes is implemented. Controlled delivery from Halloysite Nanotubes (HNT) is modeled based on interactions between the HNT's inner wall and the nanoparticles (NP) and among NPs themselves. The model was validated using experimental data published in the literature. The validated model is then used to study the effect of multiple parameters like HNT diameter and length, particle charge, ambient temperature and the creation of smart caps at the tube ends on the release of encapsulated NPs. The results show that release profiles depend on the size distribution of the HNT batch used for the experiment, as delivery is sensitive to HNT lumen and length. The effect of the addition of end-caps to the HNTs, on the rate of release of encapsulated NPs is also studied here. The results show that the release profiles are significantly affected by the addition of end caps to the HNTs and is sensitive to the end-cap pore lumen. A very good agreement with the experiment is observed when a weight

  9. Tolerability and efficacy of two synergistic ratios of oral morphine and oxycodone combinations versus morphine in patients with chronic noncancer pain.

    PubMed

    de la Iglesia, Felix A; Pace, Gary W; Robinson, Gary L W G; Huang, Nuo-Yu; Stern, Warren; Richards, Patricia

    2012-01-01

    Analgesic synergy and improved tolerability have been reported for flexible dose morphine and oxycodone combinations. This report describes two studies with similar double-blind, randomized, 7-day crossover designs (up to 7 days per arm) conducted to 1) explore the analgesic and safety benefit offixed ratio of morphine (M) and oxycodone (0) combinations (MOX) and 2) define the optimal ratio for morphine and oxycodone combination. Clinical study centers in Australia. Patients with chronic noncancer pain. Eligible patients were randomly assigned to receive flexible doses of either M or fixed ratio of MOX (M3:02 in study A; M1:02 in study B). The starting doses of M or MOX were the morphine equivalent doses (MEDs) converted from the analgesics received before entering double-blind treatment. At each crossover period, the doses were titrated to achieve analgesia at steady state, which was defined as when the same total daily dose (+/-10 percent) had been given consecutively for 3 days. The primary endpoint was the study medication dose (MED), which produced adequate pain control at steady state. Analgesic synergy in MOX was observed in both studies. On an MED basis, 61.6 percent (study A, M:0 = 3:2) or 46.8 percent (study B, M:0 = 1:2) more MED were needed forM monotherapy to achieve steady-state pain control when compared with MOX. Patient tolerability profiles were also generally better in the MOX groups. A 3:2 or 1:2 fixed ratio combination of morphine and oxycodone (MOX) produced analgesic synergy and a tolerability profile improvement in patients with chronic noncancer pain.

  10. Electrically controlled drug release from nanostructured polypyrrole coated on titanium.

    PubMed

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J

    2011-02-25

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s(-1). Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

  11. Electrically controlled drug release from nanostructured polypyrrole coated on titanium

    NASA Astrophysics Data System (ADS)

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J.

    2011-02-01

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s - 1. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

  12. Mathematical modeling of triamcinolone acetonide drug release from the I-vation intravitreal implant (a controlled release platform).

    PubMed

    Barnett, Peter J

    2009-01-01

    In-vitro drug release of triamcinolone acetonide from the I-vation implant can be controlled and tuned by varying its formulation ingredients. These release characteristics can be modeled using a parabolic partial differential equation to describe one dimensional Fickian drug diffusion in a durable polymer matrix.

  13. Evaluation of a soil incubation method to characterize nitrogen release patterns of slow- and controlled-release fertilizers.

    PubMed

    Medina, L Carolina; Sartain, Jerry B; Obreza, Thomas A; Hall, William L; Thiex, Nancy J

    2014-01-01

    Several technologies have been proposed to characterize the nutrient release patterns of slow-release fertilizers (SRF) and controlled-release fertilizers (CRF) during the last few decades. These technologies have been developed mainly by manufacturers, and are product-specific, based on the regulation and analysis of each SRF and CRF product. Despite previous efforts to characterize SRF and CRF materials, no standardized, validated method exists to assess their nutrient release patterns. However, the increased production and distribution of these materials in specialty and nonspecialty markets requires an appropriate method to verify product claims and material performance. A soil incubation column leaching procedure was evaluated to determine its suitability as a standard method to estimate nitrogen (N) release patterns of SRFs and CRFs during 180 days. The influence of three soil/sand ratios, three incubation temperatures, and four soils on method behavior was assessed using five SRFs and three CRFs. In general, the highest soil/sand ratio increased the N release rate of all materials, but this effect was more marked for the SRFs. Temperature had the greatest influence on N release rates. For CRFs, the initial N release rates and the percentage N released/day increased as temperature increased. For SRFs, raising the temperature from 25 to 35 degreesC increased initial N release rate and the total cumulative N released, and almost doubled the percentage released/day. The percentage N released/day from all products generally increased as the texture of the soil changed from sandy to loamy (lowa>California>Pennsylvania>Florida). The soil incubation technique was demonstrated to be robust and reliable for characterizing N release patterns from SRFs and CRFs. The method was reproducible, and variations in soil/sand ratio, temperature, and soil had little effect on the results.

  14. Gelatin Methacrylate Microspheres for Growth Factor Controlled Release

    PubMed Central

    Nguyen, Anh H.; McKinney, Jay; Miller, Tobias; Bongiorno, Tom; McDevitt, Todd C.

    2014-01-01

    Gelatin has been commonly used as a delivery vehicle for various biomolecules for tissue engineering and regenerative medicine applications due to its simple fabrication methods, inherent electrostatic binding properties, and proteolytic degradability. Compared to traditional chemical cross-linking methods, such as the use of glutaraldehyde (GA), methacrylate modification of gelatin offers an alternative method to better control the extent of hydrogel cross-linking. Here we examined the physical properties and growth factor delivery of gelatin methacrylate (GMA) microparticles formulated with a wide range of different cross-linking densities (15–90%). Less methacrylated MPs had decreased elastic moduli and larger mesh sizes compared to GA MPs, with increasing methacrylation correlating to greater moduli and smaller mesh sizes. As expected, an inverse correlation between microparticle cross-linking density and degradation was observed, with the lowest cross-linked GMA MPs degrading at the fastest rate, comparable to GA MPs. Interestingly, GMA MPs at lower cross-linking densities could be loaded with up to a 10-fold higher relative amount of growth factor over conventional GA cross-linked MPs, despite an order of magnitude greater gelatin content of GA MPs. Moreover, a reduced GMA cross-linking density resulted in more complete release of bone morphogenic protein 4 (BMP4) and basic fibroblast growth factor (bFGF) and accelerated release rate with collagenase treatment. These studies demonstrate that GMA MPs provide a more flexible platform for growth factor delivery by enhancing the relative binding capacity and permitting proteolytic degradation tunability, thereby offering a more potent controlled release system for growth factor delivery. PMID:25463489

  15. Controlled iodine release from polyurethane sponges for water decontamination.

    PubMed

    Aviv, Oren; Laout, Natalia; Ratner, Stanislav; Harik, Oshrat; Kunduru, Konda Reddy; Domb, Abraham J

    2013-12-28

    Iodinated polyurethane (IPU) sponges were prepared by immersing sponges in aqueous/organic solutions of iodine or exposing sponges to iodine vapors. Iodine was readily adsorbed into the polymers up to 100% (w/w). The adsorption of iodine on the surface was characterized by XPS and SEM analyses. The iodine loaded IPU sponges were coated with ethylene vinyl acetate (EVA), in order to release iodine in a controlled rate for water decontamination combined with active carbon cartridge, which adsorbs the iodine residues after the microbial inactivation. The EVA coated IPU were incorporated in a water purifier and tested for iodine release to water and for microbial inactivation efficiency according to WQA certification program against P231/EPA for 250l, using 25l a day with flow rate of 6-8min/1l. The antimicrobial activity was also studied against Escherichia coli and MS2 phage. Bacterial results exceeded the minimal requirement for bacterial removal of 6log reduction throughout the entire lifespan. At any testing point, no bacteria was detected in the outlet achieving more than 7.1 to more than 8log reduction as calculated upon the inlet concentration. Virus surrogate, MS2, reduction results varied from 4.11log reduction under tap water, and 5.11log reduction under basic water (pH9) to 1.32 for acidic water (pH5). Controlled and stable iodine release was observed with the EVA coated IPU sponges and was effective in deactivating the bacteria and virus present in the contaminated water and thus, these iodinated PU systems could be used in water purification to provide safe drinking water. These sponges may find applications as disinfectants in medicine. © 2013.

  16. Physical and chemical control of released microorganisms at field sites

    SciTech Connect

    Donegan, K.; Seidler, R.; Matyac, C.

    1991-01-01

    An important consideration in the environmental release of a genetically engineered microorganism (GEM) is the capability for reduction or elimination of GEM populations once their function is completed or if adverse environmental effects are observed. The decontamination treatments of burning and biocide application, alone and in combination with tilling, were evaluated for their ability to reduce populations of bacteria released on the phylloplane. Field plots of bush beans sprayed with the bacterium Erwinia herbicola, received the following treatments: (1) control, (2) control + till, (3) burn, (4) burn + till, (5) Kocide (cupric hydroxide), (6) Kocide + till, (7) Agri-strep (streptomycin sulfate), and (8) Agri-strept + till. Leaves and soil from the plots were sampled -1, 1, 5, 8, 12, 15, 19, and 27 days after application of the decontamination treatments. Burning produced a significant and persistent reduction in the number of bacteria whereas tilling, alone or in combination with the biocide treatments, stimulated a significant and persistent reduction in the number of bacteria, whereas tilling, alone or in combination with the biocide treatments, stimulated a significant increase in bacterial populations that persisted for several weeks.

  17. A concise review on smart polymers for controlled drug release.

    PubMed

    Aghabegi Moghanjoughi, Arezou; Khoshnevis, Dorna; Zarrabi, Ali

    2016-06-01

    Design and synthesis of efficient drug delivery systems are of critical importance in health care management. Innovations in materials chemistry especially in polymer field allows introduction of advanced drug delivery systems since polymers could provide controlled release of drugs in predetermined doses over long periods, cyclic and tunable dosages. To this end, researchers have taken advantages of smart polymers since they can undergo large reversible, chemical, or physical fluctuations as responses to small changes in environmental conditions, for instance, in pH, temperature, light, and phase transition. The present review aims to highlight various kinds of smart polymers, which are used in controlled drug delivery systems as well as mechanisms of action and their applications.

  18. Modeling controlled nutrient release from a population of polymer coated fertilizers: statistically based model for diffusion release.

    PubMed

    Shaviv, Avi; Raban, Smadar; Zaidel, Elina

    2003-05-15

    A statistically based model for describing the release from a population of polymer coated controlled release fertilizer (CRF) granules by the diffusion mechanism was constructed. The model is based on a mathematical-mechanistic description of the release from a single granule of a coated CRF accounting for its complex and nonlinear nature. The large variation within populations of coated CRFs poses the need for a statistically based approach to integrate over the release from the individual granules within a given population for which the distribution and range of granule radii and coating thickness are known. The model was constructed and verified using experimentally determined parameters and release curves of polymer-coated CRFs. A sensitivity analysis indicated the importance of water permeability in controlling the lag period and that of solute permeability in governing the rate of linear release and the total duration of the release. Increasing the mean values of normally distributed granule radii or coating thickness, increases the lag period and the period of linear release. The variation of radii and coating thickness, within realistic ranges, affects the release only when the standard deviation is very large or when water permeability is reduced without affecting solute permeability. The model provides an effective tool for designing and improving agronomic and environmental effectiveness of polymer-coated CRFs.

  19. Differential activation of the μ-opioid receptor by oxycodone and morphine in pain-related brain regions in a bone cancer pain model

    PubMed Central

    Nakamura, Atsushi; Hasegawa, Minoru; Minami, Kazuhisa; Kanbara, Tomoe; Tomii, Takako; Nishiyori, Atsushi; Narita, Minoru; Suzuki, Tsutomu; Kato, Akira

    2013-01-01

    Background and Purpose Bone cancer pain is chronic and often difficult to control with opioids. However, recent studies have shown that several opioids have distinct analgesic profiles in chronic pain. Experimental Approach To clarify the mechanisms underlying these distinct analgesic profiles, functional changes in the μ-opioid receptor were examined using a mouse femur bone cancer (FBC) model. Key Results In the FBC model, the Bmax of [3H]-DAMGO binding was reduced by 15–45% in the periaqueductal grey matter (PAG), region ventral to the PAG (vPAG), mediodorsal thalamus (mTH), ventral thalamus and spinal cord. Oxycodone (10−8–10−5 M) and morphine (10−8–10−5 M) activated [35S]-GTPγS binding, but the activation was significantly attenuated in the PAG, vPAG, mTH and spinal cord in the FBC model. Interestingly, the attenuation of oxycodone-induced [35S]-GTPγS binding was quite limited (9–26%) in comparison with that of morphine (46–65%) in the PAG, vPAG and mTH, but not in the spinal cord. Furthermore, i.c.v. oxycodone at doses of 0.02–1.0 μg per mouse clearly inhibited pain-related behaviours, such as guarding, limb-use abnormalities and allodynia-like behaviour in the FBC model mice, while i.c.v. morphine (0.05–2.0 μg per mouse) had only partial or little analgesic effect on limb-use abnormalities and allodynia-like behaviour. Conclusion and Implications These results show that μ-opioid receptor functions are attenuated in several pain-related regions in bone cancer in an agonist-dependent manner, and suggest that modification of the μ-opioid receptor is responsible for the distinct analgesic effect of oxycodone and morphine. PMID:22889192

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

    PubMed

    Gebauer, M G; McClure, A F; Vlahakis, T L

    2001-07-31

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

  1. Oxycodone/acetaminophen at low dosage: an alternative pain treatment for patients with rheumatoid arthritis.

    PubMed

    Raffaeli, William; Pari, Claudia; Corvetta, Angelo; Sarti, Donatella; Di Sabatino, Valentina; Biasi, Giovanni; Galeazzi, Maurizio

    2010-01-01

    To assess efficacy and safety of the association oxycodone/acetaminophen (oxycodone/acetaminophen) for pain treatment and disability improvement in patients with rheumatoid arthritis (RA). Patients with RA (n = 29), suffering from moderate to severe pain for more than 3 months, were included in the study, except those under RA therapy with biological drugs. The treatment started with oxycodone/acetaminophen at the dosage of 5 mg/325 mg, and then the dosage was titrated until the attainment of good pain relief. Antiemetic and laxative therapy was used for the prophylaxis of known opioid-related adverse events. Patients continued their RA therapy without changing the dosages, reported reduced pain intensity and disease activity, and improvement of disability. Forty-two percent of patients had a good clinical response to oxycodone/acetaminophen treatment, according to European League against Rheumatism (EULAR) assessment criteria, and 50 percent of patients reached the American College of Rheumatology 20 percent improvement criteria (ACR20). At the end of the study, the mean (+/- SD) daily effective oxycodone/acetaminophen dose was 13.8 (+/- 6.8) mg/720.4 (+/- 291.0) mg. No serious adverse event was observed. Nausea, vomiting, and stipsis of mild-moderate intensity were the most common adverse events. Oxycodone/acetaminophen at low dosages for the treatment of chronic pain in RA patients can be a good alternative to non-steroidal antiinflammatory drugs (NSAIDs), allowing the reduction of their consumption, while keeping RA therapy stable.

  2. Investigating the in vitro drug release kinetics from controlled release diclofenac potassium-ethocel matrix tablets and the influence of co-excipients on drug release patterns.

    PubMed

    Shah, Shefaat Ullah; Shah, Kifayat Ullah; Rehman, Asimur; Khan, Gul Majid

    2011-04-01

    The objective of the study was to formulate and evaluate controlled release polymeric tablets of Diclofenac Potassium for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with different types and grades of Ethyl Cellulose Ether derivatives in several drug-to-polymer ratios (D:P) were compressed into tablets using the direct compression method. In vitro drug release studies were performed in phosphate buffer (pH 7.4) as dissolution medium by using USP Method-1 (Rotating Basket Method). Similarity factor f2 and dissimilarity factor f1 were applied for checking the similarities and dissimilarities of the release profiles of different formulations. For the determination of the release mechanism and drug release kinetics various mathematical/kinetic models were employed. It was found that all of the Ethocel polymers could significantly slow down the drug release rate with Ethocel FP polymers being the most efficient, especially at D:P ratios of 10:03 which lead towards the achievement of zero or near zero order release kinetics.

  3. Efficacy and gastrointestinal tolerability of oral oxycodone/naloxone combination for chronic pain in outpatients with cancer: an observational study.

    PubMed

    Cuomo, Arturo; Russo, Gennaro; Esposito, Gennaro; Forte, Cira Antonietta; Connola, Marianna; Marcassa, Claudio

    2014-12-01

    Combination opioid agonist/antagonist therapy has been shown to preserve bowel function in patients with chronic cancer pain. This retrospective study evaluated the efficacy and tolerability of prolonged-released fixed-dose oxycodone-naloxone (PR OXN) in consecutive outpatients with chronic cancer pain. Of 206 patients prescribed PR OXN (mean age 61.3 ± 12.9 years; 52.9% female), 31.5% were opioid naïve. PR OXN was associated with a significant decrease in pain score measured on a visual analogue scale over 28 days (P < .0001), without adverse effects on bowel function, nor change in laxative use. PR OXN efficacy and tolerability were similar in opioid-naïve and -experienced patients, and among age-stratified subgroups. No severe side effects occurred. In a real-life outpatient setting, PR OXN provided analgesia without bowel dysfunction in patients with chronic cancer pain.

  4. Controlling Hazardous Releases while Protecting Passengers in Civil Infrastructure Systems

    NASA Astrophysics Data System (ADS)

    Rimer, Sara P.; Katopodes, Nikolaos D.

    2015-11-01

    The threat of accidental or deliberate toxic chemicals released into public spaces is a significant concern to public safety, and the real-time detection and mitigation of such hazardous contaminants has the potential to minimize harm and save lives. Furthermore, the safe evacuation of occupants during such a catastrophe is of utmost importance. This research develops a comprehensive means to address such scenarios, through both the sensing and control of contaminants, and the modeling of and potential communication to occupants as they evacuate. A computational fluid dynamics model is developed of a simplified public space characterized by a long conduit (e.g. airport terminal) with unidirectional ambient flow that is capable of detecting and mitigating the hazardous contaminant (via boundary ports) over several time horizons using model predictive control optimization. Additionally, a physical prototype is built to test the real-time feasibility of this computational flow control model. The prototype is a blower wind-tunnel with an elongated test section with the capability of sensing (via digital camera) an injected `contaminant' (propylene glycol smoke), and then mitigating that contaminant using actuators (compressed air operated vacuum nozzles) which are operated by a set of pressure regulators and a programmable controller. Finally, an agent-based model is developed to simulate ``agents'' (i.e. building occupants) as they evacuate a public space, and is coupled with the computational flow control model such that agents must interact with a dynamic, threatening environment. NSF-CMMI #0856438.

  5. Corrected QT interval prolongation after an overdose of escitalopram, morphine, oxycodone, zopiclone and benzodiazepines.

    PubMed

    Baranchuk, Adrian; Simpson, Christopher S; Methot, Michelle; Gibson, Kara; Strum, David

    2008-07-01

    Escitalopram is the recently marketed S-enantiomer of the widely used antidepressant citalopram. Data from intentional overexposure to this medication are limited. Twelve-lead electrocardiogram (ECG) effects from racemic citalopram have been described; however, the present report is the first, to the best of the authors' knowledge, that describes all the reported abnormalities in a single patient receiving escitalopram. A 52-year-old man with a history of depression treated with escitalopram 10 mg/day, extended-release morphine 30 mg/day and zopiclone 15 mg/day was found unconscious at his home. He was known to have attempted suicide three weeks previously. Partially emptied bottles of escitalopram, morphine, oxycodone, zopiclone, lorazepam and diazepam were found close to the patient. He was transferred to the emergency department, where airway management and other supportive care were initiated. The patient was transferred to the intensive care unit. The initial 12-lead ECG demonstrated junctional rhythm at 48 beats/min, a wide complex escape (145 ms) with right bundle branch morphology and a prolonged corrected QT interval at 650 ms. Cardiac monitoring was undertaken. No ventricular arrhythmias or torsade de pointes were detected. No specific treatment for shortening the QT was implemented. Another 12-lead ECG performed 48 h later demonstrated sinus tachycardia with a normal corrected QT, normal PR interval and normal QRS duration. The effects of the overdose of escitalopram on the ECG and its interactions with other drugs are reviewed.

  6. Controlled Release Pulmonary Administration of Curcumin Using Swellable Biocompatible Microparticles

    PubMed Central

    El-Sherbiny, Ibrahim M.; Smyth, Hugh D. C.

    2012-01-01

    This study involves a promising approach to achieve sustained pulmonary drug delivery. Dry powder particulate carriers were engineered to allow simultaneous aerosol lung delivery, evasion of macrophage uptake, and sustained drug release through a controlled polymeric architecture. Chitosan grafted with PEG was synthesized and characterized (FTIR, EA, DSC and 2D-XRD). Then, a series of respirable amphiphilic hydrogel microparticles were developed via spray drying of curcumin-loaded PLGA nanoparticles with chitosan-grafted-PEG or chitosan. The nano and microparticles were fully characterized using an array of physicochemical analytical methods including particle size, surface morphology, dynamic swelling, density, moisture content and biodegradation rates. The PLGA nanoparticles and the hydrogel microspheres encapsulating the curcumin-loaded PLGA nanoparticles showed average size of (221-243 nm) and (3.1-3.9 μm), respectively. The developed carriers attained high swelling within a few minutes, showed low moisture content as dry powders (0.9-1.8%), desirable biodegradation rates, high drug loading (up to 97%), and good sustained release. An aerosolization study was conducted using a next generation impactor and promising aerosolization characteristics were shown. In vitro macrophage uptake studies, cytotoxicity and in-vitro TNF-α assays were performed for the investigated particles. These assays revealed promising bio-interactions for the respirable/swellable nano-micro particles developed in this study as potential carriers for sustained pulmonary drug delivery. PMID:22136259

  7. Halloysite Nanotubes: Controlled Access and Release by Smart Gates

    PubMed Central

    Cavallaro, Giuseppe; Danilushkina, Anna A.; Evtugyn, Vladimir G.; Milioto, Stefana; Parisi, Filippo; Rozhina, Elvira V.; Fakhrullin, Rawil F.

    2017-01-01

    Hollow halloysite nanotubes have been used as nanocontainers for loading and for the triggered release of calcium hydroxide for paper preservation. A strategy for placing end-stoppers into the tubular nanocontainer is proposed and the sustained release from the cavity is reported. The incorporation of Ca(OH)2 into the nanotube lumen, as demonstrated using transmission electron microscopy (TEM) imaging and Energy Dispersive X-ray (EDX) mapping, retards the carbonatation, delaying the reaction with CO2 gas. This effect can be further controlled by placing the end-stoppers. The obtained material is tested for paper deacidification. We prove that adding halloysite filled with Ca(OH)2 to paper can reduce the impact of acid exposure on both the mechanical performance and pH alteration. The end-stoppers have a double effect: they preserve the calcium hydroxide from carbonation, and they prevent from the formation of highly basic pH and trigger the response to acid exposure minimizing the pH drop-down. These features are promising for a composite nanoadditive in the smart protection of cellulose-based materials. PMID:28788058

  8. Unconventional mechanisms control cyclic respiratory gas release in flying Drosophila.

    PubMed

    Lehmann, Fritz-Olaf; Heymann, Nicole

    2005-10-01

    The high power output of flight muscles places special demands on the respiratory gas exchange system in insects. In small insects, respiration relies on diffusion, and for elevated locomotor performance such as flight, instantaneous gas exchange rates typically co-vary with the animal's metabolic activity. By contrast, under certain conditions, instantaneous release rate of carbon dioxide from the fruit fly Drosophila flying in a virtual-reality flight arena may oscillate distinctly at low frequency (0.37+/-0.055 Hz), even though flight muscle mechanical power output requires constant metabolic activity. Cross-correlation analysis suggests that this uncoupling between respiratory and metabolic rate is not driven by conventional types of convective flow reinforcement such as abdominal pumping, but might result from two unusual mechanisms for tracheal breathing. Simplified analytical modeling of diffusive tracheal gas exchange suggests that cyclic release patterns in the insect occur as a consequence of the stochastically synchronized control of spiracle opening area by the four large thoracic spiracles. Alternatively, in-flight motion analysis of the abdomen and proboscis using infra-red video imaging suggests utilization of the proboscis extension reflex (PER) for tracheal convection. Although the respiratory benefit of synchronized spiracle opening activity in the fruit fly is unclear, proboscis-induced tracheal convection might potentially help to balance the local oxygen supply between different body compartments of the flying animal.

  9. A framework to investigate drug release variability arising from hypromellose viscosity specifications in controlled release matrix tablets.

    PubMed

    Mitchell, Shawn A; Balwinski, Karen M

    2008-06-01

    Substitution level, particle size, and molecular weight are key properties of hypromellose (HPMC) known to be important to its performance in pharmaceutical-controlled release applications. The hypromellose monographs indirectly specify acceptable ranges for the molecular weight of HPMC products, expressed as the apparent viscosity of a 2% aqueous solution. The purpose of this study was to provide a framework to systematically investigate the amount of drug release variability that might be expected for typical controlled release formulations over the monograph viscosity ranges for hypromellose. An approach to estimate the expected drug release variability was developed based on scaling laws in the literature. New experimental data were generated with pentoxifylline, theophylline, and hydrochlorothiazide as model drugs to explore the applicability of this approach to a range of formulations. This methodology predicted that drug release variability over the United States Pharmacopeia (USP) viscosity ranges would be greatest for the lower viscosity grades of hypromellose, such as E50 and K100 LV. Drug release variability due to hypromellose viscosity variations is expected to be larger for formulations having substantial contributions from erosional drug release, and smaller for formulations with a predominantly diffusional drug release mechanism. These predictions need to be validated experimentally.

  10. Thermoresponsive microcapsules for controlled release of hydrophilic cargo

    NASA Astrophysics Data System (ADS)

    Amstad, Esther; Weitz, David

    2012-02-01

    Thermoresponsive microcapsules that collapse upon increasing the temperature above their lower critical solution temperature (LCST) such as poly(N-isopropyl acrylamide) (PNIPAM) capsules are well known. However, capsules consisting of thermoresponsive polymers that possess an upper critical solution temperature (UCST) and therefore swell upon increasing the temperature above their UCST are scarce. We will present a microfluidic method to assemble thermoresponsive poly([2-(methacryloyloxy)-ethyl]-dimethyl-[3-sulfopropyl-ammoniumhzdroxide) (PMEDSH) microcapsules that have UCST. These capsules are in a collapsed state at room temperature and become highly water permeable upon increasing the temperature above the UCST. To simultaneously allow for encapsulation of hydrophilic cargo and enable the water based polymerization reaction of the PMEDSH shell, these microcapsules are assembled as water/water/oil emulsions using capillary microfluidic devices. The resulting PMEDSH microcapsules are envisaged as delivery vehicles and microreactors that allow for temperature induced controlled release of hydrophilic cargo. .

  11. Externally Controlled Triggered-Release of Drug from PLGA Micro and Nanoparticles

    PubMed Central

    Hua, Xin; Tan, Shengnan; Bandara, H. M. H. N.; Fu, Yujie; Liu, Siguo; Smyth, Hugh D. C.

    2014-01-01

    Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP) and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid) PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF). An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release. PMID:25479357

  12. Comparison in vitro felodipine release rate from the original versus generic product with controlled release of the drug.

    PubMed

    Vetchy, David; Vetcha, Martina; Rabiskova, Miloslava; Gryczova, Eva; Bartosikova, Lenka

    2007-01-01

    After patent protection of original brand is over, there are a lot of generic products occurring on the pharmaceutical market. It may be the way to reduce the price, but on the other hand, one should expect the same quality and almost identity with original brand, because the development of generic drugs is based on pharmacological properties of the original brand. The aim of this study was to compare the similarity of two products with controlled release of felodipine--generic product Presid and original brand Plendil--which are commercially available in Czech Republic, based on in vitro dissolution testing. The dissolution test in three dissolution media of increasing pH (1.2, 4.5, and 6.5) for the simulation of physiological pH within the gastrointestinal tract confirmed controlled release of felodipine from the original product Plendil ER 5 mg and Plendil ER 10 mg during the period of 24 hours. The release of felodipine from generic products Presid 5 mg and Presid 10 mg was not controlled for 24 hours as it is indicated in the information leaflet. In the generic products, felodipine release was controlled just for 12 or 18 hours and in this respect did not show similarity with the original brand. Since patients take the drug just once a day in the morning, the controlled release of felodipine, which lasts only 12 to 18 hours, can cause insufficient blood pressure control especially in the most critical morning hours and higher cardiovascular risk.

  13. Temporal control of drug release from biodegradable polymer: multicomponent diclofenac sodium releasing PLGA 80/20 rod.

    PubMed

    Nikkola, Lila; Viitanen, Petrus; Ashammakhi, Nureddin

    2009-05-01

    In our previous studies we have reported on the development of diclofenac sodium (DS) releasing rods. However, their drug release profiles were unsatisfactory. To enhance the drug release properties of the implant, we have developed a system whereby various elements can be combined into one implant. Melt extruded, self-reinforced (SR), and sterilized (S) DS-containing SR-PLGA 80/20 billets were combined to produce multicomponent implants with various compositions. These components were basically heat pressed together to form multicomponent rods. Drug release from single component and multicomponent rods was defined using a UV-Vis spectrophotometer. DS was released from individual components within 82-111 days and from multicomponent rods within 50-70 days. Thermal properties were analyzed using differential scanning calorimetry (DSC). The melting temperature (T(m)) of multicomponent implants was about 157 degrees C, change in heat fusion (DeltaH) was 13.3 J/g, and the glass transition temperature (T(g)) was 55.4 degrees C. Mechanical strength was measured for 2 weeks and it decreased from 55 to 15 MPa. In conclusion, by compression molding three components with different release rates it is possible to control the temporal release from multicomponent rods. Released DS concentrations were within range for 49-74 days depending on the fractions of individual components used.

  14. Sex differences in the pharmacokinetics, oxidative metabolism and oral bioavailability of oxycodone in the Sprague-Dawley rat.

    PubMed

    Chan, Samuel; Edwards, Stephen R; Wyse, Bruce D; Smith, Maree T

    2008-03-01

    1. The pharmacokinetics and oxidative metabolism of oxycodone were investigated following intravenous and oral administration in male and female Sprague-Dawley (SD) rats. 2. High-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-tandem mass spectrometry (MS-MS) was used to quantify plasma concentrations of oxycodone and its oxidative metabolites noroxycodone and oxymorphone following administration of single bolus intravenous (5 mg/kg) and oral (10 mg/kg) doses of oxycodone. 3. The mean (+/-SEM) clearance of intravenous oxycodone was significantly higher in male than female SD rats (4.9 +/- 0.3 vs 3.1 +/- 0.3 L/h per kg, respectively; P < 0.01). Mean areas under the plasma concentration versus time curves (AUC) for oxycodone were significantly higher in female than male SD rats following intravenous (approximately 1.6-fold; P < 0.01) and oral (approximately sevenfold; P < 0.005) administration. 4. The oral bioavailability of oxycodone was low (at 1.2 and 5.0%, respectively) in male and female SD rats, a finding consistent with high first-pass metabolism. Noroxycodone : oxycodone AUC ratios were significantly higher in male than female SD rats after intravenous (approximately 2.4-fold; P < 0.005) and oral (approximately 12-fold; P < 0.005) administration. 5. Circulating oxymorphone concentrations remained very low following both routes of administration. Noroxycodone : oxymorphone AUC ratios were greater in male than female SD rats after intravenous (approximately 13- and fivefold, respectively) and oral (approximately 90- and sixfold, respectively) administration. 6. Sex differences were apparent in the pharmacokinetics, oxidative metabolism and oral bioavailability of oxycodone. Systemic exposure to oxycodone was greater in female compared with male SD rats, whereas systemic exposure to metabolically derived noroxycodone was higher in male than female SD rats. 7. Oral administration of oxycodone to the SD rat is a poor model of the human for

  15. Analgesic studies of codeine and oxycodone in patients with cancer. I. Comparisons of oral with intramuscular codeine and of oral with intramuscular oxycodone.

    PubMed

    Beaver, W T; Wallenstein, S L; Rogers, A; Houde, R W

    1978-10-01

    The relative analgesic potency of oral and intramuscular codeine was evaluated in a double-blind crossover comparison of graded single doses in patients with chronic pain due to cancer. When both duration and intensity of analgesia are considered (total effect), oral codeine was 6/10 as potent as the intramuscular form. This is a high oral/parenteral analgesic relative potency ratio compared with morphine, metopon and oxymorphone and correlates well with the results of recent studies which have determined the oral vs. intramuscular bioavailability of codeine in man. Oral and intramuscular oxycodone were also compared in a similar patient group. Like codeine, oxycodone retained at least 1/2 of its analgesic activity when administered orally. We hypothesize that the high oral/parenteral relative potency ratios of codeine and oxycodone relative to morphine and its congeners are not due to more efficient absorption after oral administration, but rather that methylation at position 3 in codeine and oxycodone protects these drugs from rapid first-pass metabolism.

  16. Impact of Release Rates on the Effectiveness of Augmentative Biological Control Agents

    PubMed Central

    Crowder, David W.

    2007-01-01

    To access the effect of augmentative biological control agents, 31 articles were reviewed that investigated the impact of release rates of 35 augmentative biological control agents on the control of 42 arthropod pests. In 64% of the cases, the release rate of the biological control agent did not significantly affect the density or mortality of the pest insect. Results where similar when parasitoidsor predators were utilized as the natural enemy. Within any order of natural enemy, there were more cases where release rates did not affect augmentative biological control than cases where release rates were significant. There were more cases in which release rates did not affect augmentative biological control when pests were from the orders Hemiptera, Acari, or Diptera, but not with pests from the order Lepidoptera. In most cases, there was an optimal release rate that produced effective control of a pest species. This was especially true when predators were used as a biological control agent. Increasing the release rate above the optimal rate did not improve control of the pest and thus would be economically detrimental. Lower release rates were of ten optimal when biological control was used in conjunction with insecticides. In many cases, the timing and method of biological control applications were more significant factors impacting the effectiveness of biological control than the release rate. Additional factors that may limit the relative impact of release rates include natural enemy fecundity, establishment rates, prey availability, dispersal, and cannibalism. PMID:20307240

  17. Impact of release rates on the effectiveness of augmentative biological control agents.

    PubMed

    Crowder, David W

    2007-01-01

    To access the effect of augmentative biological control agents, 31 articles were reviewed that investigated the impact of release rates of 35 augmentative biological control agents on the control of 42 arthropod pests. In 64% of the cases, the release rate of the biological control agent did not significantly affect the density or mortality of the pest insect. Results where similar when parasitoids or predators were utilized as the natural enemy. Within any order of natural enemy, there were more cases where release rates did not affect augmentative biological control than cases where release rates were significant. There were more cases in which release rates did not affect augmentative biological control when pests were from the orders Hemiptera, Acari, or Diptera, but not with pests from the order Lepidoptera. In most cases, there was an optimal release rate that produced effective control of a pest species. This was especially true when predators were used as a biological control agent. Increasing the release rate above the optimal rate did not improve control of the pest and thus would be economically detrimental. Lower release rates were of ten optimal when biological control was used in conjunction with insecticides. In many cases, the timing and method of biological control applications were more significant factors impacting the effectiveness of biological control than the release rate. Additional factors that may limit the relative impact of release rates include natural enemy fecundity, establishment rates, prey availability, dispersal, and cannibalism.

  18. Radio controlled release apparatus for animal data acquisition devices

    DOEpatents

    Stamps, James Frederick

    2000-01-01

    A novel apparatus for reliably and selectively releasing a data acquisition package from an animal for recovery. The data package comprises two parts: 1) an animal data acquisition device and 2) a co-located release apparatus. One embodiment, which is useful for land animals, the release apparatus includes two major components: 1) an electronics package, comprising a receiver; a decoder comparator, having at plurality of individually selectable codes; and an actuator circuit and 2) a release device, which can be a mechanical device, which acts to release the data package from the animal. To release a data package from a particular animal, a radio transmitter sends a coded signal which is decoded to determine if the code is valid for that animal data package. Having received a valid code, the release device is activated to release the data package from the animal for subsequent recovery. A second embodiment includes floatation means and is useful for releasing animal data acquisition devices attached to sea animals. This embodiment further provides for releasing a data package underwater by employing an acoustic signal.

  19. Development of controlled release spheroids using natural polysaccharide as release modifier.

    PubMed

    Kulkarni, Giriraj T; Gowthamarajan, K; Dhobe, Rohan R; Yohanan, Fenni; Suresh, B

    2005-01-01

    A polysaccharide hydrogel was isolated from the seeds of Tamarindus indica (tamarind) and was used as release modifier for the preparation of diclofenac sodium spheroids, using extrusion-spheronization technique. The process was studied for the effect of variables to arrive at spheroids with satisfactory particle shape, size and size-distribution. The prepared spheroids were characterized for surface morphology, qualitative surface porosity, friability, bulk density, and flow properties. The in vitro release studies exhibited a zero-order release kinetics that was confirmed by Higuchi's and Peppas' models. A credible correlation was obtained among swelling index, viscosity, surface roughness of the polysaccharide, and in vitro dissolution profile of the spheroids. In the comparative bioavailability study, we found that the developed spheroids were able to sustain the drug release over 8 hr and could improve the extent of absorption and bioavailability of the drug.

  20. Complex coacervates for thermally sensitive controlled release of flavor compounds.

    PubMed

    Yeo, Yoon; Bellas, Evangelia; Firestone, William; Langer, Robert; Kohane, Daniel S

    2005-09-21

    To improve the appeal of frozen baked foods upon heating, we have encapsulated flavor oil in complex coacervate microcapsules using gelatin and gum Arabic. Variation of polyion concentrations and homogenization rate affected particle morphology, size distribution, and oil release upon heating. Release of the oil from formulations was determined by a simple spectroscopic method based on separation of oil labeled with a lipophilic dye from unaffected particles. When heated to 100 degrees C or higher, univesicular microcapsules (prepared with a lower homogenization rate) released almost all of the encapsulated oil, while multivesicular microcapsules (produced by high homogenization rates) resulted had lesser degrees of release. The oil remained encapsulated during 4 weeks of storage at 4 and -20 degrees C (freezing and thawing) but was released by exposure to 100 mM NaCl at room temperature. When particles were cooled after releasing their oil content, the oil was re-encapsulated.

  1. Controlling protein release from scaffolds using polymer blends and composites.

    PubMed

    Ginty, Patrick J; Barry, John J A; White, Lisa J; Howdle, Steve M; Shakesheff, Kevin M

    2008-01-01

    We report the development of three protein loaded polymer blend and composite materials that modify the release kinetics of the protein from poly(dl-lactic acid) (P(dl)LA) scaffolds. P(dl)LA has been combined with either poly(ethylene glycol) (PEG), poly(caprolactone) (PCL) microparticles or calcium alginate fibres using supercritical CO(2) (scCO(2)) processing to form single and dual protein release scaffolds. P(dl)LA was blended with the hydrophilic polymer PEG using scCO(2) to increase the water uptake of the resultant scaffold and modify the release kinetics of an encapsulated protein. This was demonstrated by the more rapid release of the protein when compared to the release rate from P(dl)LA only scaffolds. For the P(dl)LA/alginate scaffolds, the protein loaded alginate fibres were processed into porous protein loaded P(dl)LA scaffolds using scCO(2) to produce dual release kinetics from the scaffolds. Protein release from the hydrophilic alginate fibres was more rapid in the initial stages, complementing the slower release from the slower degrading P(dl)LA scaffolds. In contrast, when protein loaded PCL particles were loaded into P(dl)LA scaffolds, the rate of protein release was retarded from the slow degrading PCL phase.

  2. Control of arachidonic acid release in chick muscle cultures

    NASA Technical Reports Server (NTRS)

    Templeton, G. H.; Padalino, M.; Wright, W.

    1985-01-01

    Cultures from thigh muscles of 12 day old embryonic chicks are utilized to examine arachidonic release, prostaglandin (PG) biosynthesis, and protein synthesis. The preparation of the cultures is described. It is observed that exogenous arachidonic acid is formed into photsphatidylethanolamine and phosphatidylcholine, is released by a calcium ionosphere or phospholiphase simulator, and is the substrate for the biosynthesis of PG; the epidermal growth factor and PGF do not stimulate protein synthesis over the basal levels. The relationship between arachidonate release and melittin is studied. The data reveal that a change in intracellular calcium stimulates phospholiphase activity, arachidonate release, and PG synthesis in chick muscle culture.

  3. Separate and combined psychopharmacological effects of alprazolam and oxycodone in healthy volunteers

    PubMed Central

    Zacny, James P.; Paice, Judith A.; Coalson, Dennis W.

    2013-01-01

    Background There are epidemiological data indicating that medical and/or nonmedical use of prescription opioids oftentimes involves concurrent use of other substances. One of those substances is benzodiazepines. It would be of relevance to characterize the effects of an opioid and a benzodiazepine when taken together to determine if measures related to abuse liability-related effects and psychomotor performance impairment are increased compared to when the drugs are taken alone. Methods Twenty volunteers participated in a crossover, randomized, double-blind study in which they received placebo, 0.5 mg alprazolam, 10mg oxycodone, and 0.5 mg alprazolam combined with 10mg oxycodone, all p.o. Subjective, psychomotor, and physiological measures were assessed during each of the four sessions. Results Oxycodone by itself increased drug liking and “take again” ratings relative to placebo, but these ratings were not increased when oxycodone was taken with alprazolam, which by itself did not increase either of these ratings. The two drugs in combination produced stronger effects (larger in magnitude or longer lasting) than when either was taken alone on a number of measures, including psychomotor performance impairment. Conclusions In healthy volunteers, abuse liability-related subjective effects of oxycodone were not enhanced by alprazolam. There was enhanced behavioral toxicity when the drugs were taken together, and thus, this is of significant concern from a public safety standpoint. PMID:22365897

  4. Effects of different dosages of oxycodone and fentanyl on the hemodynamic changes during intubation.

    PubMed

    Park, Ki-Bum; Ann, Junggun; Lee, Haemi

    2016-08-01

    To investigate the effectiveness of oxycodone compared with fentanyl for attenuating the hemodynamic response during endotracheal intubation. This study was conducted from June 2014 to February 2015 on healthy adults undergoing general anesthesia at the Yeungnam University Hospital, Daegu, Republic of Korea. Ninety-five patients were randomly assigned to one of 3 groups to receive the following drugs; Group F: fentanyl 2 μg/kg; Group O/70: oxycodone 140 μg/kg; Group O/100: oxycodone 200 μg/kg. Five minutes after injection of the study drug, general anesthesia was induced with propofol 1.5 mg/kg and rocuronium 0.8 mg/kg. The mean blood pressure (MBP), heart rate (HR), peripheral oxygen saturation (SpO2), and bispectral index (BIS) were compared before administration of the study drug (T1), just before endotracheal intubation (T2), one minute after endotracheal intubation (T3), and 7.5 minutes after endotracheal intubation (T4). Complications were assessed. The 2 oxycodone groups showed no significant differences in MBP, HR, SpO2, and BIS compared to Group F at the time points assessed. The incidence of complications was comparable among the groups.  Oxycodone could successfully be used to attenuate the sympathetic response during anesthetic induction. The hemodynamic profiles and incidence of complications were clinically similar among the groups, but Group O/70 tended to show a lower rate of complications of apnea.

  5. Molecular Mechanisms Underlying the Enhanced Analgesic Effect of Oxycodone Compared to Morphine in Chemotherapy-Induced Neuropathic Pain

    PubMed Central

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B.; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone. PMID:24618941

  6. Molecular mechanisms underlying the enhanced analgesic effect of oxycodone compared to morphine in chemotherapy-induced neuropathic pain.

    PubMed

    Thibault, Karine; Calvino, Bernard; Rivals, Isabelle; Marchand, Fabien; Dubacq, Sophie; McMahon, Stephen B; Pezet, Sophie

    2014-01-01

    Oxycodone is a μ-opioid receptor agonist, used for the treatment of a large variety of painful disorders. Several studies have reported that oxycodone is a more potent pain reliever than morphine, and that it improves the quality of life of patients. However, the neurobiological mechanisms underlying the therapeutic action of these two opioids are only partially understood. The aim of this study was to define the molecular changes underlying the long-lasting analgesic effects of oxycodone and morphine in an animal model of peripheral neuropathy induced by a chemotherapic agent, vincristine. Using a behavioural approach, we show that oxycodone maintains an optimal analgesic effect after chronic treatment, whereas the effect of morphine dies down. In addition, using DNA microarray technology on dorsal root ganglia, we provide evidence that the long-term analgesic effect of oxycodone is due to an up-regulation in GABAB receptor expression in sensory neurons. These receptors are transported to their central terminals within the dorsal horn, and subsequently reinforce a presynaptic inhibition, since only the long-lasting (and not acute) anti-hyperalgesic effect of oxycodone was abolished by intrathecal administration of a GABAB receptor antagonist; in contrast, the morphine effect was unaffected. Our study demonstrates that the GABAB receptor is functionally required for the alleviating effect of oxycodone in neuropathic pain condition, thus providing new insight into the molecular mechanisms underlying the sustained analgesic action of oxycodone.

  7. Effect of soil moisture on the release of alachlor from alginate-based controlled-release formulations.

    PubMed

    Nasser, Ahmed; Mingelgrin, Uri; Gerstl, Zev

    2008-02-27

    The release of alachlor from controlled-release formulations (CRFs) based on alginate-montmorillonite matrices into aqueous polyethylene glycol (PEG) solutions of different concentrations and into a soil at different moisture contents was studied. In distilled water and in PEG-containing solutions displaying -0.1 MPa potential and up, the beads imbibe water and swell. The ensuing increase in weight is about 5%, and the increase in the bead's diameter is about 10%. At water potentials of -0.5 MPa and lower, loss of weight and shrinkage of the beads were observed. The changes in weight and diameter of the alginate-clay beads incubated in a Hamra loamy sand soil at 26.5% moisture content (w/w; -0.18 MPa) were similar to those observed in PEG solutions of >-0.5 MPa moisture potential. The weight and diameter losses observed in the drier soils (12.0 and 7.1% water content; -0.49 and -1.11 MPa) were similar to those in the more concentrated PEG solutions. A decrease in the rate of release of the active ingredient from the beads into soil was observed as the water potential decreased (drier soils). The release of the active ingredient from the investigated CRFs displayed a linear relationship to the square root of time, suggesting a diffusion-controlled-release rate. Data extracted from this relationship enabled the formulation of a mathematical model that correlates rate of release to water content.

  8. Understanding and Controlling iron Release in Distribution Systems

    EPA Science Inventory

    Generation of red-water resulting from the release of iron from drinking water distribution system materials is a major consumer complaint of drinking water systems. The objective of this presentation is to provide a fundamental basis for iron release from drinking water distrib...

  9. Understanding and Controlling iron Release in Distribution Systems

    EPA Science Inventory

    Generation of red-water resulting from the release of iron from drinking water distribution system materials is a major consumer complaint of drinking water systems. The objective of this presentation is to provide a fundamental basis for iron release from drinking water distrib...

  10. Controlled release of free-falling test models

    NASA Technical Reports Server (NTRS)

    Fife, W. J.; Holway, H. P.

    1970-01-01

    Releasing device, powered by a drill motor through an adjustable speed reducer, has a spinning release head with three retractable spring-loaded fingers. The fingers are retracted by manual triggering of a cable at the motor end of the unit.

  11. Method of achieving the controlled release of thermonuclear energy

    DOEpatents

    Brueckner, Keith A.

    1986-01-01

    A method of achieving the controlled release of thermonuclear energy by illuminating a minute, solid density, hollow shell of a mixture of material such as deuterium and tritium with a high intensity, uniformly converging laser wave to effect an extremely rapid build-up of energy in inwardly traveling shock waves to implode the shell creating thermonuclear conditions causing a reaction of deuterons and tritons and a resultant high energy thermonuclear burn. Utilizing the resulting energy as a thermal source and to breed tritium or plutonium. The invention also contemplates a laser source wherein the flux level is increased with time to reduce the initial shock heating of fuel and provide maximum compression after implosion; and, in addition, computations and an equation are provided to enable the selection of a design having a high degree of stability and a dependable fusion performance by establishing a proper relationship between the laser energy input and the size and character of the selected material for the fusion capsule.

  12. Controlled release: a cultural analysis of collegiate polydrug use.

    PubMed

    Quintero, Gilbert

    2009-03-01

    Social science research on polydrug use among young adult college students is scant, adopts definitions of this practice that are often devoid of sociocultural context, and emphasizes a very narrow range of use patterns. This article, based on ethnographic interviews from a study of collegiate prescription drug misuse, expands this focus by offering a cultural analysis of polydrug use. Two specific types of collegiate polydrug use, simultaneous interaction and sequential management, are examined within a cultural framework that relates these practices to the expression of two complementary values--control and release. The college experience provides young people with a culturally sanctioned "time-out" period that affords freedom from many of the roles, responsibilities, and other constraints that come to structure later adult life. At the same time, college students are expected to meet academic and social demands that require organization, initiative, and direction. Specific types of polydrug use provide young adults with a means to navigate these competing prescriptions that are characteristic of contemporary college life.

  13. Novel anhydrous emulsions: formulation as controlled release vehicles.

    PubMed

    Suitthimeathegorn, Orawan; Jaitely, Vikas; Florence, Alexander T

    2005-07-25

    Novel anhydrous emulsions, which may offer some advantages as depot or reservoir vehicles for lipophilic drugs in controlled delivery systems, were formulated using castor oil as the disperse phase and dimethicone or cyclopentasiloxane as the continuous phase. Among the emulsifiers studied only silicone surfactants (cyclomethicone/dimethicone copolyols) which were miscible in silicone oil stabilized the emulsions. Cyclomethicone/PEG/PPG-18/18 Dimethicone and Cyclopentasiloxane/PEG/PPG-18/18 Dimethicone were more effective in lowering the interfacial tension between castor oil and both dimethicone and cyclopentasiloxane. Emulsions formulated using either of these two surfactants were found to be stable against phase separation and exhibited least globule growth over 168 h. The average particle size was found to be 2-6 microm in these systems formed by probe sonication. Slow release patterns of 3H-dehydroepiandrosterone (DHEA) and 3H-dexamethasone solubilized in the disperse castor oil phase into an aqueous dialyzing medium were observed over 48 h.

  14. Controlled release of NSAIDs bound to polyacrylic carrier systems.

    PubMed

    Parejo, C; Gallardo, A; San Román, J

    1998-12-01

    The synthesis, characterization and properties of new acrylic "polymeric drugs" derived from the NSAIDs agents ibuprofen and ketoprofen are described. The swelling behavior in hydrated medium and the controlled release from hydrophilic copolymers of the NSAIDs derivatives and 2-hydroxyethylmethacrylate, HEMA, are discussed, considering the hydrolytical reactivity of the acrylamide or acrylic ester functional groups, the aromatic or aliphatic structure of the spacer side groups, and the hydrophilic character of the copolymer systems. The results obtained demonstrated that the swelling degree of copolymers depends on the average composition of copolymers, decreasing with the increase of the average fraction of the corresponding acrylic derivative of ibuprofen or ketoprofen in the copolymer system. In addition, polymers which support the NSAIDs active component through aromatic amide links, are more sensitive to hydrolytical processes than those of alkyl ester functions. The results obtained demonstrate that these supports could be applied for direct administration, transdermal, systemic or intra-articular injection, as well as in the form of films on wounds.

  15. Remotely Triggered Scaffolds for Controlled Release of Pharmaceuticals

    PubMed Central

    Roach, Paul; McGarvey, David J.; Lees, Martin R.; Hoskins, Clare

    2013-01-01

    Fe3O4-Au hybrid nanoparticles (HNPs) have shown increasing potential for biomedical applications such as image guided stimuli responsive drug delivery. Incorporation of the unique properties of HNPs into thermally responsive scaffolds holds great potential for future biomedical applications. Here we successfully fabricated smart scaffolds based on thermo-responsive poly(N-isopropylacrylamide) (pNiPAM). Nanoparticles providing localized trigger of heating when irradiated with a short laser burst were found to give rise to remote control of bulk polymer shrinkage. Gold-coated iron oxide nanoparticles were synthesized using wet chemical precipitation methods followed by electrochemical coating. After subsequent functionalization of particles with allyl methyl sulfide, mercaptodecane, cysteamine and poly(ethylene glycol) thiol to enhance stability, detailed biological safety was determined using live/dead staining and cell membrane integrity studies through lactate dehydrogenase (LDH) quantification. The PEG coated HNPs did not show significant cytotoxic effect or adverse cellular response on exposure to 7F2 cells (p < 0.05) and were carried forward for scaffold incorporation. The pNiPAM-HNP composite scaffolds were investigated for their potential as thermally triggered systems using a Q-switched Nd:YAG laser. These studies show that incorporation of HNPs resulted in scaffold deformation after very short irradiation times (seconds) due to internal structural heating. Our data highlights the potential of these hybrid-scaffold constructs for exploitation in drug delivery, using methylene blue as a model drug being released during remote structural change of the scaffold. PMID:23603890

  16. The Disposition of Oxycodone and Metabolite in Human Hair.

    PubMed

    Reisfield, Gary M; Jones, Joseph T

    2015-01-01

    The disposition of oxycodone (OC) and metabolites in hair remains poorly characterized. We present a case involving a pharmacist in an impaired professionals' monitoring program in whom hair testing yielded OC on two occasions. On both occasions, his hair was negative for the oxymorphone (OM) metabolite at the cutoff concentration of 100 pg/mg. He claimed that, absent the detection of metabolite, the OC necessarily represented external contamination. This prompted a review of the laboratory's OC-positive hair results for the quarter April-June 2014. Overall, 466 specimens contained OC, with a mean (median) concentration of 2,375 (1,060) pg/mg. Of these OC-positive specimens, only 47 (10%) contained detectable OM. When OC was present at or below the mean (median) concentration, only 2.2% (1.3%) of specimens were OM-positive. In the setting of OC administration, the detection of OM in hair is unlikely at a cutoff concentration of 100 pg/mg. More consistent demonstration of OC metabolite(s) in hair will require the validation of methods to detect OM at lower concentrations and/or methods to detect noroxycodone.

  17. [Rate of controlled-release urea pervasion through membrane determined by ultraviolet spectrophotometry].

    PubMed

    Zuo, Xiu-jin; Wang, Zhen-xin; Dai, Xiao-min; Zhou, Yi; Ma, Xiao-jun

    2006-06-01

    Application of controlled-release nitrogenous fertilizers can improve the efficiency of fertilizers and reduce the environmental pollution. Controlled-release urea (coated urea) is one of the controlled-release nitrogenous fertilizers developed quickly in the recent years. The rate of controlled-release urea pervasion through membrane is the most important index of the capacity of controlled release. There is a maximum absorption at lambda=426 nm with complex in acidic solution, using p-dimethylaminozenzaldehyde as color reagent, and the absorbance exhibits a linear reponses to the urea concentration over the range of 7.5-210 microg x mL(-1). The method for determining the rate of controlled-release urea pervasion through membrane was realized through determining the content of urea in the liquor, the recovery efficiency of the method is 96.1%-103.9%.

  18. Poly(lactic-co-glycolic) acid-controlled-release systems: experimental and modeling insights.

    PubMed

    Hines, Daniel J; Kaplan, David L

    2013-01-01

    Poly(lactic-co-glycolic acid) (PLGA) has been the most successful polymeric biomaterial used in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in the formulation of drug release devices. Mathematical modeling is a useful tool for identifying, characterizing, and predicting mechanisms of controlled release. The advantages and limitations of poly(lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled-release technology that utilize PLGA. Mathematical modeling applied toward controlled-release rates from PLGA-based devices also will be discussed to provide a complete picture of a state-of-the-art understanding of the control that can be achieved with this polymeric system, as well as the limitations.

  19. Poly (lactic-co-glycolic acid) controlled release systems: experimental and modeling insights

    PubMed Central

    Hines, Daniel J.; Kaplan, David L.

    2013-01-01

    Poly-lactic-co-glycolic acid (PLGA) has been the most successful polymeric biomaterial for use in controlled drug delivery systems. There are several different chemical and physical properties of PLGA that impact the release behavior of drugs from PLGA delivery devices. These properties must be considered and optimized in drug release device formulation. Mathematical modeling is a useful tool for identifying, characterizing, and predicting the mechanisms of controlled release. The advantages and limitations of poly (lactic-co-glycolic acid) for controlled release are reviewed, followed by a review of current approaches in controlled release technology that utilize PLGA. Mathematical modeling applied towards controlled release rates from PLGA-based devices will also be discussed to provide a complete picture of state of the art understanding of the control achievable with this polymeric system, as well as the limitations. PMID:23614648

  20. Controlled-release NPK fertilizer encapsulated by polymeric membranes.

    PubMed