Observations on the Metabolism of Morphine to Hydromorphone in Pain Patients
Morphine is one of several opioids used to treat chronic pain. Because of its high abuse potential, urine drug tests can confirm "consistency with prescribed medications." Hydromorphone is a recently described minor metabolite of morphine, but few data exist on the characteristics of this...
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| Veröffentlicht in: | Journal of analytical toxicology 2012-05, Vol.36 (4), p.250-256 |
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| creator | Hughes, Michelle M. Atayee, Rabia S. Best, Brookie M. Pesce, Amadeo J. |
| description | Morphine is one of several opioids used to treat chronic pain. Because of its high abuse potential, urine drug tests can confirm "consistency with prescribed medications." Hydromorphone is a recently described minor metabolite of morphine, but few data exist on the characteristics of this metabolic pathway or the relationship of morphine and hydromorphone between and within subjects. Part I of this retrospective study shows that formation of hydromorphone from morphine is concentration-dependent and possibly saturated at high concentrations of morphine. In addition, the percentage of ultra-rapid metabolizers and poor metabolizers can be determined using the lower asymptote of a sigmoidal mathematical fit and are estimated to be 0.63 and 4.0%, respectively. Expected limits of morphine and hydromorphone (as a result of morphine metabolism) concentrations in the urine were established. Part II of this study used the metabolic ratio (hydromorphone-morphine) to determine the inter-patient and intra-patient variability in morphine metabolism to hydromorphone. Metabolic ratio values varied over a large range; 25-fold and 7-fold, respectively. The expected limits established in this study can assist in assessing the cause for possible variances in metabolism, such as drug interactions. The wide variability between and within subjects may explain unpredictable, adverse effects. |
| doi_str_mv | 10.1093/jat/bks021 |
| format | Article |
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Because of its high abuse potential, urine drug tests can confirm "consistency with prescribed medications." Hydromorphone is a recently described minor metabolite of morphine, but few data exist on the characteristics of this metabolic pathway or the relationship of morphine and hydromorphone between and within subjects. Part I of this retrospective study shows that formation of hydromorphone from morphine is concentration-dependent and possibly saturated at high concentrations of morphine. In addition, the percentage of ultra-rapid metabolizers and poor metabolizers can be determined using the lower asymptote of a sigmoidal mathematical fit and are estimated to be 0.63 and 4.0%, respectively. Expected limits of morphine and hydromorphone (as a result of morphine metabolism) concentrations in the urine were established. Part II of this study used the metabolic ratio (hydromorphone-morphine) to determine the inter-patient and intra-patient variability in morphine metabolism to hydromorphone. Metabolic ratio values varied over a large range; 25-fold and 7-fold, respectively. The expected limits established in this study can assist in assessing the cause for possible variances in metabolism, such as drug interactions. The wide variability between and within subjects may explain unpredictable, adverse effects.</description><identifier>ISSN: 0146-4760</identifier><identifier>EISSN: 1945-2403</identifier><identifier>DOI: 10.1093/jat/bks021</identifier><identifier>PMID: 22511699</identifier><identifier>CODEN: JATOD3</identifier><language>eng</language><publisher>Niles, IL: Oxford University Press</publisher><subject>Analgesics, Opioid - pharmacokinetics ; Analgesics, Opioid - therapeutic use ; Analysis ; Biological and medical sciences ; Chromatography, High Pressure Liquid ; Chronic Pain - drug therapy ; Chronic Pain - metabolism ; Data processing ; Databases, Factual ; Dose-Response Relationship, Drug ; Drug abuse ; Drug interaction ; Drug metabolism ; General pharmacology ; Humans ; Hydromorphone - metabolism ; Mass Spectrometry ; Medical sciences ; Metabolic pathways ; Metabolites ; Morphine ; Morphine - pharmacokinetics ; Morphine - therapeutic use ; Opioids ; Pain ; Pharmacology. Drug treatments ; Retrospective Studies ; Side effects ; Time Factors ; Urine</subject><ispartof>Journal of analytical toxicology, 2012-05, Vol.36 (4), p.250-256</ispartof><rights>The Author [2012]. Published by Oxford University Press. All rights reserved. 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Because of its high abuse potential, urine drug tests can confirm "consistency with prescribed medications." Hydromorphone is a recently described minor metabolite of morphine, but few data exist on the characteristics of this metabolic pathway or the relationship of morphine and hydromorphone between and within subjects. Part I of this retrospective study shows that formation of hydromorphone from morphine is concentration-dependent and possibly saturated at high concentrations of morphine. In addition, the percentage of ultra-rapid metabolizers and poor metabolizers can be determined using the lower asymptote of a sigmoidal mathematical fit and are estimated to be 0.63 and 4.0%, respectively. Expected limits of morphine and hydromorphone (as a result of morphine metabolism) concentrations in the urine were established. Part II of this study used the metabolic ratio (hydromorphone-morphine) to determine the inter-patient and intra-patient variability in morphine metabolism to hydromorphone. Metabolic ratio values varied over a large range; 25-fold and 7-fold, respectively. The expected limits established in this study can assist in assessing the cause for possible variances in metabolism, such as drug interactions. The wide variability between and within subjects may explain unpredictable, adverse effects.</description><subject>Analgesics, Opioid - pharmacokinetics</subject><subject>Analgesics, Opioid - therapeutic use</subject><subject>Analysis</subject><subject>Biological and medical sciences</subject><subject>Chromatography, High Pressure Liquid</subject><subject>Chronic Pain - drug therapy</subject><subject>Chronic Pain - metabolism</subject><subject>Data processing</subject><subject>Databases, Factual</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug abuse</subject><subject>Drug interaction</subject><subject>Drug metabolism</subject><subject>General pharmacology</subject><subject>Humans</subject><subject>Hydromorphone - metabolism</subject><subject>Mass Spectrometry</subject><subject>Medical sciences</subject><subject>Metabolic pathways</subject><subject>Metabolites</subject><subject>Morphine</subject><subject>Morphine - pharmacokinetics</subject><subject>Morphine - therapeutic use</subject><subject>Opioids</subject><subject>Pain</subject><subject>Pharmacology. Drug treatments</subject><subject>Retrospective Studies</subject><subject>Side effects</subject><subject>Time Factors</subject><subject>Urine</subject><issn>0146-4760</issn><issn>1945-2403</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0E1Lw0AQBuBFFFurF3-A5CKIEDv7kd3sUYpaoaUe9Bw2yYZuTbJ1dyP035vaWm96mYHhYYZ5EbrEcIdB0vFKhXH-7oHgIzTEkiUxYUCP0RAw4zETHAbozPsVAOYpp6doQEiCMZdyiGaL3Gv3qYKxrY9sG4WljuY6qNzWxjeRraK5deulaXUUbDTdlM4224HtB6aNXtR3CUa3wZ-jk0rVXl_s-wi9PT68TqbxbPH0PLmfxQXDPMQFxSQvhQQMWBIBkCSMCEW44lRRBioRCaO5IESISooEylwqkFiUpNJYpXSEbnZ7185-dNqHrDG-0HWtWm07n2EiiKBpysX_FIAIyVLBe3q7o4Wz3jtdZWtnGuU2Pcq2QWd90Nku6B5f7fd2eaPLA_1JtgfXe6B8oerKqbYw_tclKVDav3lwtlv_dfALUYaQ6w</recordid><startdate>20120501</startdate><enddate>20120501</enddate><creator>Hughes, Michelle M.</creator><creator>Atayee, Rabia S.</creator><creator>Best, Brookie M.</creator><creator>Pesce, Amadeo J.</creator><general>Oxford University Press</general><general>Preston Publications</general><scope>IQODW</scope><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>7X8</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>20120501</creationdate><title>Observations on the Metabolism of Morphine to Hydromorphone in Pain Patients</title><author>Hughes, Michelle M. ; Atayee, Rabia S. ; Best, Brookie M. ; Pesce, Amadeo J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c416t-c312bd7901019270055427a26a63a340a57543b72277f9750db9a0917d2fe1a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Analgesics, Opioid - pharmacokinetics</topic><topic>Analgesics, Opioid - therapeutic use</topic><topic>Analysis</topic><topic>Biological and medical sciences</topic><topic>Chromatography, High Pressure Liquid</topic><topic>Chronic Pain - drug therapy</topic><topic>Chronic Pain - metabolism</topic><topic>Data processing</topic><topic>Databases, Factual</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug abuse</topic><topic>Drug interaction</topic><topic>Drug metabolism</topic><topic>General pharmacology</topic><topic>Humans</topic><topic>Hydromorphone - metabolism</topic><topic>Mass Spectrometry</topic><topic>Medical sciences</topic><topic>Metabolic pathways</topic><topic>Metabolites</topic><topic>Morphine</topic><topic>Morphine - pharmacokinetics</topic><topic>Morphine - therapeutic use</topic><topic>Opioids</topic><topic>Pain</topic><topic>Pharmacology. Drug treatments</topic><topic>Retrospective Studies</topic><topic>Side effects</topic><topic>Time Factors</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hughes, Michelle M.</creatorcontrib><creatorcontrib>Atayee, Rabia S.</creatorcontrib><creatorcontrib>Best, Brookie M.</creatorcontrib><creatorcontrib>Pesce, Amadeo J.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Journal of analytical toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hughes, Michelle M.</au><au>Atayee, Rabia S.</au><au>Best, Brookie M.</au><au>Pesce, Amadeo J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Observations on the Metabolism of Morphine to Hydromorphone in Pain Patients</atitle><jtitle>Journal of analytical toxicology</jtitle><addtitle>J Anal Toxicol</addtitle><date>2012-05-01</date><risdate>2012</risdate><volume>36</volume><issue>4</issue><spage>250</spage><epage>256</epage><pages>250-256</pages><issn>0146-4760</issn><eissn>1945-2403</eissn><coden>JATOD3</coden><abstract>Morphine is one of several opioids used to treat chronic pain. Because of its high abuse potential, urine drug tests can confirm "consistency with prescribed medications." Hydromorphone is a recently described minor metabolite of morphine, but few data exist on the characteristics of this metabolic pathway or the relationship of morphine and hydromorphone between and within subjects. Part I of this retrospective study shows that formation of hydromorphone from morphine is concentration-dependent and possibly saturated at high concentrations of morphine. In addition, the percentage of ultra-rapid metabolizers and poor metabolizers can be determined using the lower asymptote of a sigmoidal mathematical fit and are estimated to be 0.63 and 4.0%, respectively. Expected limits of morphine and hydromorphone (as a result of morphine metabolism) concentrations in the urine were established. Part II of this study used the metabolic ratio (hydromorphone-morphine) to determine the inter-patient and intra-patient variability in morphine metabolism to hydromorphone. Metabolic ratio values varied over a large range; 25-fold and 7-fold, respectively. The expected limits established in this study can assist in assessing the cause for possible variances in metabolism, such as drug interactions. The wide variability between and within subjects may explain unpredictable, adverse effects.</abstract><cop>Niles, IL</cop><pub>Oxford University Press</pub><pmid>22511699</pmid><doi>10.1093/jat/bks021</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Analgesics, Opioid - pharmacokinetics Analgesics, Opioid - therapeutic use Analysis Biological and medical sciences Chromatography, High Pressure Liquid Chronic Pain - drug therapy Chronic Pain - metabolism Data processing Databases, Factual Dose-Response Relationship, Drug Drug abuse Drug interaction Drug metabolism General pharmacology Humans Hydromorphone - metabolism Mass Spectrometry Medical sciences Metabolic pathways Metabolites Morphine Morphine - pharmacokinetics Morphine - therapeutic use Opioids Pain Pharmacology. Drug treatments Retrospective Studies Side effects Time Factors Urine |
| title | Observations on the Metabolism of Morphine to Hydromorphone in Pain Patients |
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