Efficacy and Safety of Lubiprostone in Patients with Opioid-Induced Constipation: Phase 3 Study Results and Pooled Analysis of the Effect of Concomitant Methadone Use on Clinical Outcomes
Abstract Objective The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo-controlled study. These data were also pooled with those from two similar phase 3...
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| Veröffentlicht in: | Pain medicine (Malden, Mass.) Mass.), 2018-06, Vol.19 (6), p.1184-1194 |
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| creator | Spierings, Egilius L H Drossman, Douglas A Cryer, Byron Mazen Jamal, M Losch-Beridon, Taryn Mareya, Shadreck M Wang, Martin |
| description | Abstract
Objective
The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo-controlled study. These data were also pooled with those from two similar phase 3 studies to explore the effects of methadone on treatment response.
Methods
In the primary study, adults with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were randomized to receive lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary end point was a change from baseline in the frequency of SBMs at week 8 in patients without a prior dose reduction. For the pooled analysis, the efficacy of lubiprostone was compared with placebo in patients receiving methadone or nonmethadone opioids. Responders were defined as patients with nine or more weeks of nonmissing SBM data who had one or more additional SBMs per week from baseline for each week that data were available and three or more SBMs per week for nine or more weeks.
Results
In the primary study, the change from baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo groups (P = 0.842). In the pooled analysis, the response rate was significantly higher with lubiprostone treatment vs placebo for patients receiving nonmethadone opioids (P = 0.002) but was similar between lubiprostone treatment and placebo in patients receiving methadone (P = 0.692). The safety profile of lubiprostone was unaffected by methadone use.
Conclusions
The phase 3 study did not meet its primary efficacy end point. However, analysis of pooled data from all phase 3 studies in the OIC clinical development program, stratified by methadone opioid usage, confirmed that lubiprostone is effective for treatment of OIC in patients taking nonmethadone opioids; no safety concerns were identified based on the type of opioid used. |
| doi_str_mv | 10.1093/pm/pnx156 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_1950164306</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A588341829</galeid><oup_id>10.1093/pm/pnx156</oup_id><sourcerecordid>A588341829</sourcerecordid><originalsourceid>FETCH-LOGICAL-c444t-6daebd27d59681a14ea91c2944d8c7337917cc8ff967dd2c71fd397c60e481a63</originalsourceid><addsrcrecordid>eNp9kk1v1DAQhiMEoh9w4A8gS3Aoh23jjzgxt9WqQKVFu6L0bHntMesqsdPYEeS38edwtAsIhJAPHlvPvDN-PUXxApeXuBT0qu-uev8NV_xRcYorwheM0_rxMSa0rk6KsxjvyxJz1tCnxQkROWx4c1p8v7bWaaUnpLxBt8pCmlCwaD3uXD-EmIIH5DzaquTAp4i-urRHm94FZxY33owaDFoFH5PrMxL8W7TdqwiIots0mgl9gji2OW-W34bQZnzpVTtFF-c6aQ8otwA6zacspEPnkvIJfYS0V2Yuf5flgker1vncaos2Y8oUxGfFE6vaCM-P-3lx9-768-rDYr15f7NarheaMZYW3CjYGVKbSvAGK8xACayJYMw0uqa0FrjWurFW8NoYomtsDRW15iWwzHN6XlwcdLMhDyPEJDsXNbSt8hDGKLGoZmdpOaOv_kLvwzjk90ZJcEm4IKJiv6kvqgXpvA1pUHoWlcuqaSjDDRGZuvwHlZeBzulsjHX5_o-EN4cEnT8uDmBlP7hODZPEpZwHRfadPAxKZl8eGx13HZhf5M_JyMDrAxDG_j86PwB1KMZS</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2102692954</pqid></control><display><type>article</type><title>Efficacy and Safety of Lubiprostone in Patients with Opioid-Induced Constipation: Phase 3 Study Results and Pooled Analysis of the Effect of Concomitant Methadone Use on Clinical Outcomes</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Spierings, Egilius L H ; Drossman, Douglas A ; Cryer, Byron ; Mazen Jamal, M ; Losch-Beridon, Taryn ; Mareya, Shadreck M ; Wang, Martin</creator><creatorcontrib>Spierings, Egilius L H ; Drossman, Douglas A ; Cryer, Byron ; Mazen Jamal, M ; Losch-Beridon, Taryn ; Mareya, Shadreck M ; Wang, Martin</creatorcontrib><description>Abstract
Objective
The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo-controlled study. These data were also pooled with those from two similar phase 3 studies to explore the effects of methadone on treatment response.
Methods
In the primary study, adults with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were randomized to receive lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary end point was a change from baseline in the frequency of SBMs at week 8 in patients without a prior dose reduction. For the pooled analysis, the efficacy of lubiprostone was compared with placebo in patients receiving methadone or nonmethadone opioids. Responders were defined as patients with nine or more weeks of nonmissing SBM data who had one or more additional SBMs per week from baseline for each week that data were available and three or more SBMs per week for nine or more weeks.
Results
In the primary study, the change from baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo groups (P = 0.842). In the pooled analysis, the response rate was significantly higher with lubiprostone treatment vs placebo for patients receiving nonmethadone opioids (P = 0.002) but was similar between lubiprostone treatment and placebo in patients receiving methadone (P = 0.692). The safety profile of lubiprostone was unaffected by methadone use.
Conclusions
The phase 3 study did not meet its primary efficacy end point. However, analysis of pooled data from all phase 3 studies in the OIC clinical development program, stratified by methadone opioid usage, confirmed that lubiprostone is effective for treatment of OIC in patients taking nonmethadone opioids; no safety concerns were identified based on the type of opioid used.</description><identifier>ISSN: 1526-2375</identifier><identifier>EISSN: 1526-4637</identifier><identifier>DOI: 10.1093/pm/pnx156</identifier><identifier>PMID: 29016868</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Adult ; Analgesics, Opioid - adverse effects ; Central nervous system depressants ; Chloride Channel Agonists - therapeutic use ; Chronic pain ; Chronic Pain - drug therapy ; Clinical outcomes ; Clinical trials ; Constipation ; Constipation - chemically induced ; Constipation - drug therapy ; Data processing ; Double-Blind Method ; Effectiveness ; Female ; Humans ; Intestine ; Lubiprostone ; Lubiprostone - therapeutic use ; Male ; Methadone ; Methadone - adverse effects ; Middle Aged ; Narcotics ; Opioids ; Patient outcomes ; Patients ; Safety ; Side effects</subject><ispartof>Pain medicine (Malden, Mass.), 2018-06, Vol.19 (6), p.1184-1194</ispartof><rights>2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2017</rights><rights>COPYRIGHT 2018 Oxford University Press</rights><rights>Copyright © 2017 American Academy of Pain Medicine</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c444t-6daebd27d59681a14ea91c2944d8c7337917cc8ff967dd2c71fd397c60e481a63</citedby><cites>FETCH-LOGICAL-c444t-6daebd27d59681a14ea91c2944d8c7337917cc8ff967dd2c71fd397c60e481a63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,1581,27911,27912</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29016868$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Spierings, Egilius L H</creatorcontrib><creatorcontrib>Drossman, Douglas A</creatorcontrib><creatorcontrib>Cryer, Byron</creatorcontrib><creatorcontrib>Mazen Jamal, M</creatorcontrib><creatorcontrib>Losch-Beridon, Taryn</creatorcontrib><creatorcontrib>Mareya, Shadreck M</creatorcontrib><creatorcontrib>Wang, Martin</creatorcontrib><title>Efficacy and Safety of Lubiprostone in Patients with Opioid-Induced Constipation: Phase 3 Study Results and Pooled Analysis of the Effect of Concomitant Methadone Use on Clinical Outcomes</title><title>Pain medicine (Malden, Mass.)</title><addtitle>Pain Med</addtitle><description>Abstract
Objective
The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo-controlled study. These data were also pooled with those from two similar phase 3 studies to explore the effects of methadone on treatment response.
Methods
In the primary study, adults with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were randomized to receive lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary end point was a change from baseline in the frequency of SBMs at week 8 in patients without a prior dose reduction. For the pooled analysis, the efficacy of lubiprostone was compared with placebo in patients receiving methadone or nonmethadone opioids. Responders were defined as patients with nine or more weeks of nonmissing SBM data who had one or more additional SBMs per week from baseline for each week that data were available and three or more SBMs per week for nine or more weeks.
Results
In the primary study, the change from baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo groups (P = 0.842). In the pooled analysis, the response rate was significantly higher with lubiprostone treatment vs placebo for patients receiving nonmethadone opioids (P = 0.002) but was similar between lubiprostone treatment and placebo in patients receiving methadone (P = 0.692). The safety profile of lubiprostone was unaffected by methadone use.
Conclusions
The phase 3 study did not meet its primary efficacy end point. However, analysis of pooled data from all phase 3 studies in the OIC clinical development program, stratified by methadone opioid usage, confirmed that lubiprostone is effective for treatment of OIC in patients taking nonmethadone opioids; no safety concerns were identified based on the type of opioid used.</description><subject>Adult</subject><subject>Analgesics, Opioid - adverse effects</subject><subject>Central nervous system depressants</subject><subject>Chloride Channel Agonists - therapeutic use</subject><subject>Chronic pain</subject><subject>Chronic Pain - drug therapy</subject><subject>Clinical outcomes</subject><subject>Clinical trials</subject><subject>Constipation</subject><subject>Constipation - chemically induced</subject><subject>Constipation - drug therapy</subject><subject>Data processing</subject><subject>Double-Blind Method</subject><subject>Effectiveness</subject><subject>Female</subject><subject>Humans</subject><subject>Intestine</subject><subject>Lubiprostone</subject><subject>Lubiprostone - therapeutic use</subject><subject>Male</subject><subject>Methadone</subject><subject>Methadone - adverse effects</subject><subject>Middle Aged</subject><subject>Narcotics</subject><subject>Opioids</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Safety</subject><subject>Side effects</subject><issn>1526-2375</issn><issn>1526-4637</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kk1v1DAQhiMEoh9w4A8gS3Aoh23jjzgxt9WqQKVFu6L0bHntMesqsdPYEeS38edwtAsIhJAPHlvPvDN-PUXxApeXuBT0qu-uev8NV_xRcYorwheM0_rxMSa0rk6KsxjvyxJz1tCnxQkROWx4c1p8v7bWaaUnpLxBt8pCmlCwaD3uXD-EmIIH5DzaquTAp4i-urRHm94FZxY33owaDFoFH5PrMxL8W7TdqwiIots0mgl9gji2OW-W34bQZnzpVTtFF-c6aQ8otwA6zacspEPnkvIJfYS0V2Yuf5flgker1vncaos2Y8oUxGfFE6vaCM-P-3lx9-768-rDYr15f7NarheaMZYW3CjYGVKbSvAGK8xACayJYMw0uqa0FrjWurFW8NoYomtsDRW15iWwzHN6XlwcdLMhDyPEJDsXNbSt8hDGKLGoZmdpOaOv_kLvwzjk90ZJcEm4IKJiv6kvqgXpvA1pUHoWlcuqaSjDDRGZuvwHlZeBzulsjHX5_o-EN4cEnT8uDmBlP7hODZPEpZwHRfadPAxKZl8eGx13HZhf5M_JyMDrAxDG_j86PwB1KMZS</recordid><startdate>20180601</startdate><enddate>20180601</enddate><creator>Spierings, Egilius L H</creator><creator>Drossman, Douglas A</creator><creator>Cryer, Byron</creator><creator>Mazen Jamal, M</creator><creator>Losch-Beridon, Taryn</creator><creator>Mareya, Shadreck M</creator><creator>Wang, Martin</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20180601</creationdate><title>Efficacy and Safety of Lubiprostone in Patients with Opioid-Induced Constipation: Phase 3 Study Results and Pooled Analysis of the Effect of Concomitant Methadone Use on Clinical Outcomes</title><author>Spierings, Egilius L H ; Drossman, Douglas A ; Cryer, Byron ; Mazen Jamal, M ; Losch-Beridon, Taryn ; Mareya, Shadreck M ; Wang, Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c444t-6daebd27d59681a14ea91c2944d8c7337917cc8ff967dd2c71fd397c60e481a63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Analgesics, Opioid - adverse effects</topic><topic>Central nervous system depressants</topic><topic>Chloride Channel Agonists - therapeutic use</topic><topic>Chronic pain</topic><topic>Chronic Pain - drug therapy</topic><topic>Clinical outcomes</topic><topic>Clinical trials</topic><topic>Constipation</topic><topic>Constipation - chemically induced</topic><topic>Constipation - drug therapy</topic><topic>Data processing</topic><topic>Double-Blind Method</topic><topic>Effectiveness</topic><topic>Female</topic><topic>Humans</topic><topic>Intestine</topic><topic>Lubiprostone</topic><topic>Lubiprostone - therapeutic use</topic><topic>Male</topic><topic>Methadone</topic><topic>Methadone - adverse effects</topic><topic>Middle Aged</topic><topic>Narcotics</topic><topic>Opioids</topic><topic>Patient outcomes</topic><topic>Patients</topic><topic>Safety</topic><topic>Side effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Spierings, Egilius L H</creatorcontrib><creatorcontrib>Drossman, Douglas A</creatorcontrib><creatorcontrib>Cryer, Byron</creatorcontrib><creatorcontrib>Mazen Jamal, M</creatorcontrib><creatorcontrib>Losch-Beridon, Taryn</creatorcontrib><creatorcontrib>Mareya, Shadreck M</creatorcontrib><creatorcontrib>Wang, Martin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Pain medicine (Malden, Mass.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Spierings, Egilius L H</au><au>Drossman, Douglas A</au><au>Cryer, Byron</au><au>Mazen Jamal, M</au><au>Losch-Beridon, Taryn</au><au>Mareya, Shadreck M</au><au>Wang, Martin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and Safety of Lubiprostone in Patients with Opioid-Induced Constipation: Phase 3 Study Results and Pooled Analysis of the Effect of Concomitant Methadone Use on Clinical Outcomes</atitle><jtitle>Pain medicine (Malden, Mass.)</jtitle><addtitle>Pain Med</addtitle><date>2018-06-01</date><risdate>2018</risdate><volume>19</volume><issue>6</issue><spage>1184</spage><epage>1194</epage><pages>1184-1194</pages><issn>1526-2375</issn><eissn>1526-4637</eissn><abstract>Abstract
Objective
The efficacy and safety of oral lubiprostone for relieving symptoms of opioid-induced constipation (OIC) in patients with chronic noncancer pain were evaluated in a randomized, double-blind, placebo-controlled study. These data were also pooled with those from two similar phase 3 studies to explore the effects of methadone on treatment response.
Methods
In the primary study, adults with OIC (fewer than three spontaneous bowel movements [SBMs] per week) were randomized to receive lubiprostone 24 mcg or placebo twice daily for 12 weeks. The primary end point was a change from baseline in the frequency of SBMs at week 8 in patients without a prior dose reduction. For the pooled analysis, the efficacy of lubiprostone was compared with placebo in patients receiving methadone or nonmethadone opioids. Responders were defined as patients with nine or more weeks of nonmissing SBM data who had one or more additional SBMs per week from baseline for each week that data were available and three or more SBMs per week for nine or more weeks.
Results
In the primary study, the change from baseline at week 8 in SBM frequency was similar in the lubiprostone and placebo groups (P = 0.842). In the pooled analysis, the response rate was significantly higher with lubiprostone treatment vs placebo for patients receiving nonmethadone opioids (P = 0.002) but was similar between lubiprostone treatment and placebo in patients receiving methadone (P = 0.692). The safety profile of lubiprostone was unaffected by methadone use.
Conclusions
The phase 3 study did not meet its primary efficacy end point. However, analysis of pooled data from all phase 3 studies in the OIC clinical development program, stratified by methadone opioid usage, confirmed that lubiprostone is effective for treatment of OIC in patients taking nonmethadone opioids; no safety concerns were identified based on the type of opioid used.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>29016868</pmid><doi>10.1093/pm/pnx156</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Pain medicine (Malden, Mass.), 2018-06, Vol.19 (6), p.1184-1194 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Adult Analgesics, Opioid - adverse effects Central nervous system depressants Chloride Channel Agonists - therapeutic use Chronic pain Chronic Pain - drug therapy Clinical outcomes Clinical trials Constipation Constipation - chemically induced Constipation - drug therapy Data processing Double-Blind Method Effectiveness Female Humans Intestine Lubiprostone Lubiprostone - therapeutic use Male Methadone Methadone - adverse effects Middle Aged Narcotics Opioids Patient outcomes Patients Safety Side effects |
| title | Efficacy and Safety of Lubiprostone in Patients with Opioid-Induced Constipation: Phase 3 Study Results and Pooled Analysis of the Effect of Concomitant Methadone Use on Clinical Outcomes |
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