Cancer Cachexia Raises the Plasma Concentration of Oxymorphone Through the Reduction of CYP3A But Not CYP2D6 in Oxycodone-Treated Patients
This study evaluated the plasma concentrations of oxycodone and its demethylates and opioid‐induced adverse effects based on cachexia stage in cancer patients receiving oxycodone. Seventy patients receiving oxycodone for cancer pain were enrolled. Cachexia was evaluated using the Glasgow Prognostic...
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| Veröffentlicht in: | Journal of clinical pharmacology 2013-08, Vol.53 (8), p.812-818 |
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| creator | Naito, Takafumi Tashiro, Masaki Ishida, Takuya Ohnishi, Kazunori Kawakami, Junichi |
| description | This study evaluated the plasma concentrations of oxycodone and its demethylates and opioid‐induced adverse effects based on cachexia stage in cancer patients receiving oxycodone. Seventy patients receiving oxycodone for cancer pain were enrolled. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined at the titration dose. Opioid‐induced adverse effects were monitored for 2 weeks after the titration. Plasma concentrations of oxycodone and oxymorphone but not noroxycodone in patients with a GPS of 2 were significantly higher than that with a GPS of 0. The metabolic ratios of noroxycodone but not oxymorphone to oxycodone in patients with a GPS of 1 and 2 were significantly lower than in those with a GPS of 0. A higher GPS was associated with a higher incidence of somnolence, while the GPS did not affect the incidence of vomiting. Plasma concentrations of oxycodone and oxymorphone were not associated with the incidence of adverse effects. In conclusion, cancer cachexia raised the plasma exposures of oxycodone and oxymorphone through the reduction of CYP3A but not CYP2D6. Although the cachexia elevated the incidence of somnolence, alterations in their pharmacokinetics were not associated with the incidence. |
| doi_str_mv | 10.1002/jcph.112 |
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Seventy patients receiving oxycodone for cancer pain were enrolled. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined at the titration dose. Opioid‐induced adverse effects were monitored for 2 weeks after the titration. Plasma concentrations of oxycodone and oxymorphone but not noroxycodone in patients with a GPS of 2 were significantly higher than that with a GPS of 0. The metabolic ratios of noroxycodone but not oxymorphone to oxycodone in patients with a GPS of 1 and 2 were significantly lower than in those with a GPS of 0. A higher GPS was associated with a higher incidence of somnolence, while the GPS did not affect the incidence of vomiting. Plasma concentrations of oxycodone and oxymorphone were not associated with the incidence of adverse effects. In conclusion, cancer cachexia raised the plasma exposures of oxycodone and oxymorphone through the reduction of CYP3A but not CYP2D6. Although the cachexia elevated the incidence of somnolence, alterations in their pharmacokinetics were not associated with the incidence.</description><identifier>ISSN: 0091-2700</identifier><identifier>EISSN: 1552-4604</identifier><identifier>DOI: 10.1002/jcph.112</identifier><identifier>PMID: 23733622</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Aged ; Analgesics, Opioid - blood ; Analgesics, Opioid - pharmacokinetics ; Analgesics, Opioid - therapeutic use ; Cachexia - blood ; Cachexia - drug therapy ; Cachexia - etiology ; Cancer ; cancer cachexia ; CYP2D6 ; Cytochrome P-450 CYP2D6 - metabolism ; Cytochrome P-450 CYP3A - metabolism ; Female ; Humans ; Male ; Middle Aged ; Morphinans - blood ; Narcotics ; Neoplasms - blood ; Neoplasms - complications ; Neoplasms - drug therapy ; oxycodone ; Oxycodone - blood ; Oxycodone - pharmacokinetics ; Oxycodone - therapeutic use ; oxymorphone ; Oxymorphone - blood ; Pain - blood ; Pain - drug therapy ; pharmacokinetics ; Plasma</subject><ispartof>Journal of clinical pharmacology, 2013-08, Vol.53 (8), p.812-818</ispartof><rights>The Author(s) 2013</rights><rights>2013 American College of Clinical Pharmacology</rights><rights>The Author(s) 2013.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3992-5d1219e24bb80c178828f0d8de3b4258eb88e63e4823630987b6c7596a5625ca3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcph.112$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcph.112$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23733622$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Naito, Takafumi</creatorcontrib><creatorcontrib>Tashiro, Masaki</creatorcontrib><creatorcontrib>Ishida, Takuya</creatorcontrib><creatorcontrib>Ohnishi, Kazunori</creatorcontrib><creatorcontrib>Kawakami, Junichi</creatorcontrib><title>Cancer Cachexia Raises the Plasma Concentration of Oxymorphone Through the Reduction of CYP3A But Not CYP2D6 in Oxycodone-Treated Patients</title><title>Journal of clinical pharmacology</title><addtitle>The Journal of Clinical Pharmacology</addtitle><description>This study evaluated the plasma concentrations of oxycodone and its demethylates and opioid‐induced adverse effects based on cachexia stage in cancer patients receiving oxycodone. Seventy patients receiving oxycodone for cancer pain were enrolled. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined at the titration dose. Opioid‐induced adverse effects were monitored for 2 weeks after the titration. Plasma concentrations of oxycodone and oxymorphone but not noroxycodone in patients with a GPS of 2 were significantly higher than that with a GPS of 0. The metabolic ratios of noroxycodone but not oxymorphone to oxycodone in patients with a GPS of 1 and 2 were significantly lower than in those with a GPS of 0. A higher GPS was associated with a higher incidence of somnolence, while the GPS did not affect the incidence of vomiting. Plasma concentrations of oxycodone and oxymorphone were not associated with the incidence of adverse effects. In conclusion, cancer cachexia raised the plasma exposures of oxycodone and oxymorphone through the reduction of CYP3A but not CYP2D6. Although the cachexia elevated the incidence of somnolence, alterations in their pharmacokinetics were not associated with the incidence.</description><subject>Aged</subject><subject>Analgesics, Opioid - blood</subject><subject>Analgesics, Opioid - pharmacokinetics</subject><subject>Analgesics, Opioid - therapeutic use</subject><subject>Cachexia - blood</subject><subject>Cachexia - drug therapy</subject><subject>Cachexia - etiology</subject><subject>Cancer</subject><subject>cancer cachexia</subject><subject>CYP2D6</subject><subject>Cytochrome P-450 CYP2D6 - metabolism</subject><subject>Cytochrome P-450 CYP3A - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Morphinans - blood</subject><subject>Narcotics</subject><subject>Neoplasms - blood</subject><subject>Neoplasms - complications</subject><subject>Neoplasms - drug therapy</subject><subject>oxycodone</subject><subject>Oxycodone - blood</subject><subject>Oxycodone - pharmacokinetics</subject><subject>Oxycodone - therapeutic use</subject><subject>oxymorphone</subject><subject>Oxymorphone - blood</subject><subject>Pain - blood</subject><subject>Pain - drug therapy</subject><subject>pharmacokinetics</subject><subject>Plasma</subject><issn>0091-2700</issn><issn>1552-4604</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkd1u1DAQhSMEoktB4gmQJW64SRn_xHEuS6BdUNUu1aKKK8tJZkm22XhrO-ruK_DUOHRbJOZmNKPvHI3mJMlbCicUgH1c19v2hFL2LJnRLGOpkCCeJzOAgqYsBzhKXnm_BqBSZPRlcsR4zrlkbJb8Ls1QoyOlqVvcdYZcm86jJ6FFsuiN3xhS2kgMwZnQ2YHYFbna7TfWbVs7IFm2zo6_2r_8NTZj_QiVPxf8lHwaA7m0YZrYZ0m6YRLXtonSdOnQBGzIIhpHf_86ebEyvcc3h36c_Dj7sizn6cXV-dfy9CKteVGwNGsoowUyUVUKaporxdQKGtUgrwTLFFZKoeQoFOOSQ6HyStZ5VkiTSZbVhh8nHx58t87ejeiD3nS-xr43A9rRayoAeKGYyCP6_j90bUc3xOs0zUGqnMV_RurdgRqrDTZ667qNcXv9-OUIiAfg3vYBnb_tx3t0ukXTh1ZDLBFDShlQDipO6bSaZOlB1vW4f7KloKfQ9RS6jqHrb-ViHvs_vvMBd0-8cbda5jzP9M3luRbf53C2LKi-4X8APHyoqA</recordid><startdate>201308</startdate><enddate>201308</enddate><creator>Naito, Takafumi</creator><creator>Tashiro, Masaki</creator><creator>Ishida, Takuya</creator><creator>Ohnishi, Kazunori</creator><creator>Kawakami, Junichi</creator><general>Blackwell Publishing Ltd</general><general>American College of Clinical Pharmacology</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201308</creationdate><title>Cancer Cachexia Raises the Plasma Concentration of Oxymorphone Through the Reduction of CYP3A But Not CYP2D6 in Oxycodone-Treated Patients</title><author>Naito, Takafumi ; Tashiro, Masaki ; Ishida, Takuya ; Ohnishi, Kazunori ; Kawakami, Junichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3992-5d1219e24bb80c178828f0d8de3b4258eb88e63e4823630987b6c7596a5625ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aged</topic><topic>Analgesics, Opioid - blood</topic><topic>Analgesics, Opioid - pharmacokinetics</topic><topic>Analgesics, Opioid - therapeutic use</topic><topic>Cachexia - blood</topic><topic>Cachexia - drug therapy</topic><topic>Cachexia - etiology</topic><topic>Cancer</topic><topic>cancer cachexia</topic><topic>CYP2D6</topic><topic>Cytochrome P-450 CYP2D6 - metabolism</topic><topic>Cytochrome P-450 CYP3A - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Morphinans - blood</topic><topic>Narcotics</topic><topic>Neoplasms - blood</topic><topic>Neoplasms - complications</topic><topic>Neoplasms - drug therapy</topic><topic>oxycodone</topic><topic>Oxycodone - blood</topic><topic>Oxycodone - pharmacokinetics</topic><topic>Oxycodone - therapeutic use</topic><topic>oxymorphone</topic><topic>Oxymorphone - blood</topic><topic>Pain - blood</topic><topic>Pain - drug therapy</topic><topic>pharmacokinetics</topic><topic>Plasma</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Naito, Takafumi</creatorcontrib><creatorcontrib>Tashiro, Masaki</creatorcontrib><creatorcontrib>Ishida, Takuya</creatorcontrib><creatorcontrib>Ohnishi, Kazunori</creatorcontrib><creatorcontrib>Kawakami, Junichi</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Naito, Takafumi</au><au>Tashiro, Masaki</au><au>Ishida, Takuya</au><au>Ohnishi, Kazunori</au><au>Kawakami, Junichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cancer Cachexia Raises the Plasma Concentration of Oxymorphone Through the Reduction of CYP3A But Not CYP2D6 in Oxycodone-Treated Patients</atitle><jtitle>Journal of clinical pharmacology</jtitle><addtitle>The Journal of Clinical Pharmacology</addtitle><date>2013-08</date><risdate>2013</risdate><volume>53</volume><issue>8</issue><spage>812</spage><epage>818</epage><pages>812-818</pages><issn>0091-2700</issn><eissn>1552-4604</eissn><abstract>This study evaluated the plasma concentrations of oxycodone and its demethylates and opioid‐induced adverse effects based on cachexia stage in cancer patients receiving oxycodone. Seventy patients receiving oxycodone for cancer pain were enrolled. Cachexia was evaluated using the Glasgow Prognostic Score (GPS). Predose plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined at the titration dose. Opioid‐induced adverse effects were monitored for 2 weeks after the titration. Plasma concentrations of oxycodone and oxymorphone but not noroxycodone in patients with a GPS of 2 were significantly higher than that with a GPS of 0. The metabolic ratios of noroxycodone but not oxymorphone to oxycodone in patients with a GPS of 1 and 2 were significantly lower than in those with a GPS of 0. A higher GPS was associated with a higher incidence of somnolence, while the GPS did not affect the incidence of vomiting. Plasma concentrations of oxycodone and oxymorphone were not associated with the incidence of adverse effects. In conclusion, cancer cachexia raised the plasma exposures of oxycodone and oxymorphone through the reduction of CYP3A but not CYP2D6. Although the cachexia elevated the incidence of somnolence, alterations in their pharmacokinetics were not associated with the incidence.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>23733622</pmid><doi>10.1002/jcph.112</doi><tpages>7</tpages></addata></record> |
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| subjects | Aged Analgesics, Opioid - blood Analgesics, Opioid - pharmacokinetics Analgesics, Opioid - therapeutic use Cachexia - blood Cachexia - drug therapy Cachexia - etiology Cancer cancer cachexia CYP2D6 Cytochrome P-450 CYP2D6 - metabolism Cytochrome P-450 CYP3A - metabolism Female Humans Male Middle Aged Morphinans - blood Narcotics Neoplasms - blood Neoplasms - complications Neoplasms - drug therapy oxycodone Oxycodone - blood Oxycodone - pharmacokinetics Oxycodone - therapeutic use oxymorphone Oxymorphone - blood Pain - blood Pain - drug therapy pharmacokinetics Plasma |
| title | Cancer Cachexia Raises the Plasma Concentration of Oxymorphone Through the Reduction of CYP3A But Not CYP2D6 in Oxycodone-Treated Patients |
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