Altered Morphine Glucuronide and Bile Acid Disposition in Patients with Non-Alcoholic Steatohepatitis
The functional impact of altered drug transport protein expression on the systemic pharmacokinetics of morphine, hepatically-derived morphine glucuronide (morphine-3- and morphine-6-glucuronide), and fasting bile acids was evaluated in patients with biopsy-confirmed non-alcoholic steatohepatitis (NA...
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| Veröffentlicht in: | Clinical pharmacology and therapeutics 2015-03, Vol.97 (4), p.419-427 |
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| container_end_page | 427 |
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| container_issue | 4 |
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| container_title | Clinical pharmacology and therapeutics |
| container_volume | 97 |
| creator | Ferslew, Brian C. Johnston, Curtis K. Tsakalozou, Eleftheria Bridges, Arlene S. Paine, Mary F. Jia, Wei Stewart, Paul W. Barritt, A. Sidney Brouwer, Kim L.R. |
| description | The functional impact of altered drug transport protein expression on the systemic pharmacokinetics of morphine, hepatically-derived morphine glucuronide (morphine-3- and morphine-6-glucuronide), and fasting bile acids was evaluated in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH) compared to healthy subjects. The maximum concentration (C
max
) and area under the concentration-time curve (AUC
0-last
) of morphine glucuronide in serum were increased in NASH patients (343 vs. 225nM and 58.8 vs. 37.2μM*min, respectively;
P
≤0.005); morphine pharmacokinetics did not differ between groups. Linear regression analyses detected an association of NASH severity with increased morphine glucuronide C
max
and AUC
0-last
(
P |
| doi_str_mv | 10.1002/cpt.66 |
| format | Article |
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max
) and area under the concentration-time curve (AUC
0-last
) of morphine glucuronide in serum were increased in NASH patients (343 vs. 225nM and 58.8 vs. 37.2μM*min, respectively;
P
≤0.005); morphine pharmacokinetics did not differ between groups. Linear regression analyses detected an association of NASH severity with increased morphine glucuronide C
max
and AUC
0-last
(
P
<0.001). Fasting serum glycocholate, taurocholate and total bile acid concentrations were associated with NASH severity (
P
<0.006). Increased hepatic basolateral efflux of morphine glucuronide and bile acids is consistent with altered hepatic transport protein expression in patients with NASH and may partially explain differences in efficacy and/or toxicity of some highly transported anionic drugs/metabolites in this patient population.</description><identifier>ISSN: 0009-9236</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1002/cpt.66</identifier><identifier>PMID: 25669174</identifier><language>eng</language><ispartof>Clinical pharmacology and therapeutics, 2015-03, Vol.97 (4), p.419-427</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids></links><search><creatorcontrib>Ferslew, Brian C.</creatorcontrib><creatorcontrib>Johnston, Curtis K.</creatorcontrib><creatorcontrib>Tsakalozou, Eleftheria</creatorcontrib><creatorcontrib>Bridges, Arlene S.</creatorcontrib><creatorcontrib>Paine, Mary F.</creatorcontrib><creatorcontrib>Jia, Wei</creatorcontrib><creatorcontrib>Stewart, Paul W.</creatorcontrib><creatorcontrib>Barritt, A. Sidney</creatorcontrib><creatorcontrib>Brouwer, Kim L.R.</creatorcontrib><title>Altered Morphine Glucuronide and Bile Acid Disposition in Patients with Non-Alcoholic Steatohepatitis</title><title>Clinical pharmacology and therapeutics</title><description>The functional impact of altered drug transport protein expression on the systemic pharmacokinetics of morphine, hepatically-derived morphine glucuronide (morphine-3- and morphine-6-glucuronide), and fasting bile acids was evaluated in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH) compared to healthy subjects. The maximum concentration (C
max
) and area under the concentration-time curve (AUC
0-last
) of morphine glucuronide in serum were increased in NASH patients (343 vs. 225nM and 58.8 vs. 37.2μM*min, respectively;
P
≤0.005); morphine pharmacokinetics did not differ between groups. Linear regression analyses detected an association of NASH severity with increased morphine glucuronide C
max
and AUC
0-last
(
P
<0.001). Fasting serum glycocholate, taurocholate and total bile acid concentrations were associated with NASH severity (
P
<0.006). Increased hepatic basolateral efflux of morphine glucuronide and bile acids is consistent with altered hepatic transport protein expression in patients with NASH and may partially explain differences in efficacy and/or toxicity of some highly transported anionic drugs/metabolites in this patient population.</description><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNqljM1OxCAURonROPXvGe4LdIT-4LAxqTrqRmOi-wbhaq9hgADV-PZ24ca1q5Mv58th7EzwteC8OTexrKXcY5Xo26aWfdvvs4pzrmrVtHLFjnL-WGanNptDtmp6KZW46CqGgyuY0MJDSHEij3DnZjOn4MkiaG_hihzCYMjCDeUYMhUKHsjDky6EvmT4ojLBY_D14EyYgiMDzwV1CRPG5VMon7CDN-0ynv7ymF3ebl-u7-s4v-7QmiWTtBtjop1O32PQNP41nqbxPXyOXadUK0T778APP1dkgA</recordid><startdate>20150315</startdate><enddate>20150315</enddate><creator>Ferslew, Brian C.</creator><creator>Johnston, Curtis K.</creator><creator>Tsakalozou, Eleftheria</creator><creator>Bridges, Arlene S.</creator><creator>Paine, Mary F.</creator><creator>Jia, Wei</creator><creator>Stewart, Paul W.</creator><creator>Barritt, A. Sidney</creator><creator>Brouwer, Kim L.R.</creator><scope>5PM</scope></search><sort><creationdate>20150315</creationdate><title>Altered Morphine Glucuronide and Bile Acid Disposition in Patients with Non-Alcoholic Steatohepatitis</title><author>Ferslew, Brian C. ; Johnston, Curtis K. ; Tsakalozou, Eleftheria ; Bridges, Arlene S. ; Paine, Mary F. ; Jia, Wei ; Stewart, Paul W. ; Barritt, A. Sidney ; Brouwer, Kim L.R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmedcentral_primary_oai_pubmedcentral_nih_gov_44993113</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ferslew, Brian C.</creatorcontrib><creatorcontrib>Johnston, Curtis K.</creatorcontrib><creatorcontrib>Tsakalozou, Eleftheria</creatorcontrib><creatorcontrib>Bridges, Arlene S.</creatorcontrib><creatorcontrib>Paine, Mary F.</creatorcontrib><creatorcontrib>Jia, Wei</creatorcontrib><creatorcontrib>Stewart, Paul W.</creatorcontrib><creatorcontrib>Barritt, A. Sidney</creatorcontrib><creatorcontrib>Brouwer, Kim L.R.</creatorcontrib><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ferslew, Brian C.</au><au>Johnston, Curtis K.</au><au>Tsakalozou, Eleftheria</au><au>Bridges, Arlene S.</au><au>Paine, Mary F.</au><au>Jia, Wei</au><au>Stewart, Paul W.</au><au>Barritt, A. Sidney</au><au>Brouwer, Kim L.R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered Morphine Glucuronide and Bile Acid Disposition in Patients with Non-Alcoholic Steatohepatitis</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><date>2015-03-15</date><risdate>2015</risdate><volume>97</volume><issue>4</issue><spage>419</spage><epage>427</epage><pages>419-427</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><abstract>The functional impact of altered drug transport protein expression on the systemic pharmacokinetics of morphine, hepatically-derived morphine glucuronide (morphine-3- and morphine-6-glucuronide), and fasting bile acids was evaluated in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH) compared to healthy subjects. The maximum concentration (C
max
) and area under the concentration-time curve (AUC
0-last
) of morphine glucuronide in serum were increased in NASH patients (343 vs. 225nM and 58.8 vs. 37.2μM*min, respectively;
P
≤0.005); morphine pharmacokinetics did not differ between groups. Linear regression analyses detected an association of NASH severity with increased morphine glucuronide C
max
and AUC
0-last
(
P
<0.001). Fasting serum glycocholate, taurocholate and total bile acid concentrations were associated with NASH severity (
P
<0.006). Increased hepatic basolateral efflux of morphine glucuronide and bile acids is consistent with altered hepatic transport protein expression in patients with NASH and may partially explain differences in efficacy and/or toxicity of some highly transported anionic drugs/metabolites in this patient population.</abstract><pmid>25669174</pmid><doi>10.1002/cpt.66</doi></addata></record> |
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| ispartof | Clinical pharmacology and therapeutics, 2015-03, Vol.97 (4), p.419-427 |
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| language | eng |
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| source | Wiley Online Library Journals Frontfile Complete |
| title | Altered Morphine Glucuronide and Bile Acid Disposition in Patients with Non-Alcoholic Steatohepatitis |
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