Identification and Mechanistic Investigation of Drug-Drug Interactions Associated With Myopathy: A Translational Approach
Myopathy is a group of muscle diseases that can be induced or exacerbated by drug–drug interactions (DDIs). We sought to identify clinically important myopathic DDIs and elucidate their underlying mechanisms. Five DDIs were found to increase the risk of myopathy based on analysis of observational da...
Gespeichert in:
| Veröffentlicht in: | Clinical pharmacology and therapeutics 2015-09, Vol.98 (3), p.321-327 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 327 |
|---|---|
| container_issue | 3 |
| container_start_page | 321 |
| container_title | Clinical pharmacology and therapeutics |
| container_volume | 98 |
| creator | Han, X Quinney, SK Wang, Z Zhang, P Duke, J Desta, Z Elmendorf, JS Flockhart, DA Li, L |
| description | Myopathy is a group of muscle diseases that can be induced or exacerbated by drug–drug interactions (DDIs). We sought to identify clinically important myopathic DDIs and elucidate their underlying mechanisms. Five DDIs were found to increase the risk of myopathy based on analysis of observational data from the Indiana Network of Patient Care. Loratadine interacted with simvastatin (relative risk 95% confidence interval [CI] = [1.39, 2.06]), alprazolam (1.50, 2.31), ropinirole (2.06, 5.00), and omeprazole (1.15, 1.38). Promethazine interacted with tegaserod (1.94, 4.64). In vitro investigation showed that these DDIs were unlikely to result from inhibition of drug metabolism by CYP450 enzymes or from inhibition of hepatic uptake via the membrane transporter OATP1B1/1B3. However, we did observe in vitro synergistic myotoxicity of simvastatin and desloratadine, suggesting a role in loratadine–simvastatin interaction. This interaction was epidemiologically confirmed (odds ratio 95% CI = [2.02, 3.65]) using the data from the US Food and Drug Administration Adverse Event Reporting System. |
| doi_str_mv | 10.1002/cpt.150 |
| format | Article |
| fullrecord | <record><control><sourceid>istex_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4664558</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>ark_67375_WNG_N33JGKM4_N</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4430-48b07efa9b87e7f663c0b3436b218326c5541c7c8bb6c71aa7f96d9695dc76b03</originalsourceid><addsrcrecordid>eNp1kU1v0zAchy3ExLoN8Q2QbxxQNjt-SzggVWV0Heu2Q9GO1j-O0xiyJLKzQb497gLVOOziF_0eP5Z_RugdJaeUkPTM9MMpFeQVmlHB0kQKJl6jGSEkT_KUyUN0FMKPuOV5lr1Bh6nIlciomKFxVdp2cJUzMLiuxdCWeG1NDa0LgzN41T7auNhOaVfhL_5hm-yGGA3Wg9kFAc9D6IyDwZb4zg01Xo9dD0M9fsJzvPHQhubJAA2e973vwNQn6KCCJti3f-dj9P3r-WZxkVzdLFeL-VViOGck4VlBlK0gLzJlVSUlM6RgnMkipRlLpRGCU6NMVhTSKAqgqlyWucxFaZQsCDtGnydv_1Dc29LE53podO_dPfhRd-D0_0nrar3tHjWXkguRRcGHSWB8F4K31f4sJXrXvo7t69h-JN8_v2rP_as7Ah8n4Jdr7PiSRy9uN5Mumej4Ffb3ngb_U0vFlNB310t9zdjl8tuax8Ufd8OgPw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Identification and Mechanistic Investigation of Drug-Drug Interactions Associated With Myopathy: A Translational Approach</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Han, X ; Quinney, SK ; Wang, Z ; Zhang, P ; Duke, J ; Desta, Z ; Elmendorf, JS ; Flockhart, DA ; Li, L</creator><creatorcontrib>Han, X ; Quinney, SK ; Wang, Z ; Zhang, P ; Duke, J ; Desta, Z ; Elmendorf, JS ; Flockhart, DA ; Li, L</creatorcontrib><description>Myopathy is a group of muscle diseases that can be induced or exacerbated by drug–drug interactions (DDIs). We sought to identify clinically important myopathic DDIs and elucidate their underlying mechanisms. Five DDIs were found to increase the risk of myopathy based on analysis of observational data from the Indiana Network of Patient Care. Loratadine interacted with simvastatin (relative risk 95% confidence interval [CI] = [1.39, 2.06]), alprazolam (1.50, 2.31), ropinirole (2.06, 5.00), and omeprazole (1.15, 1.38). Promethazine interacted with tegaserod (1.94, 4.64). In vitro investigation showed that these DDIs were unlikely to result from inhibition of drug metabolism by CYP450 enzymes or from inhibition of hepatic uptake via the membrane transporter OATP1B1/1B3. However, we did observe in vitro synergistic myotoxicity of simvastatin and desloratadine, suggesting a role in loratadine–simvastatin interaction. This interaction was epidemiologically confirmed (odds ratio 95% CI = [2.02, 3.65]) using the data from the US Food and Drug Administration Adverse Event Reporting System.</description><identifier>ISSN: 0009-9236</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1002/cpt.150</identifier><identifier>PMID: 25975815</identifier><language>eng</language><publisher>United States: Blackwell Publishing Ltd</publisher><subject>Adverse Drug Reaction Reporting Systems ; Animals ; Biological Transport ; Biotransformation ; Cell Line ; Cytochrome P-450 Enzyme Inhibitors - adverse effects ; Cytochrome P-450 Enzyme Inhibitors - pharmacokinetics ; Dose-Response Relationship, Drug ; Drug Interactions ; Drug Synergism ; Drug-Related Side Effects and Adverse Reactions - diagnosis ; Drug-Related Side Effects and Adverse Reactions - epidemiology ; Drug-Related Side Effects and Adverse Reactions - etiology ; Drug-Related Side Effects and Adverse Reactions - metabolism ; Humans ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - pathology ; Muscular Diseases - chemically induced ; Muscular Diseases - diagnosis ; Muscular Diseases - epidemiology ; Muscular Diseases - metabolism ; Odds Ratio ; Organic Anion Transporters - antagonists & inhibitors ; Organic Anion Transporters - metabolism ; Rats ; Risk Assessment ; Risk Factors ; Translational Medical Research - methods ; United States - epidemiology ; United States Food and Drug Administration</subject><ispartof>Clinical pharmacology and therapeutics, 2015-09, Vol.98 (3), p.321-327</ispartof><rights>2015 The American Society for Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4430-48b07efa9b87e7f663c0b3436b218326c5541c7c8bb6c71aa7f96d9695dc76b03</citedby><cites>FETCH-LOGICAL-c4430-48b07efa9b87e7f663c0b3436b218326c5541c7c8bb6c71aa7f96d9695dc76b03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcpt.150$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcpt.150$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25975815$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, X</creatorcontrib><creatorcontrib>Quinney, SK</creatorcontrib><creatorcontrib>Wang, Z</creatorcontrib><creatorcontrib>Zhang, P</creatorcontrib><creatorcontrib>Duke, J</creatorcontrib><creatorcontrib>Desta, Z</creatorcontrib><creatorcontrib>Elmendorf, JS</creatorcontrib><creatorcontrib>Flockhart, DA</creatorcontrib><creatorcontrib>Li, L</creatorcontrib><title>Identification and Mechanistic Investigation of Drug-Drug Interactions Associated With Myopathy: A Translational Approach</title><title>Clinical pharmacology and therapeutics</title><addtitle>Clin. Pharmacol. Ther</addtitle><description>Myopathy is a group of muscle diseases that can be induced or exacerbated by drug–drug interactions (DDIs). We sought to identify clinically important myopathic DDIs and elucidate their underlying mechanisms. Five DDIs were found to increase the risk of myopathy based on analysis of observational data from the Indiana Network of Patient Care. Loratadine interacted with simvastatin (relative risk 95% confidence interval [CI] = [1.39, 2.06]), alprazolam (1.50, 2.31), ropinirole (2.06, 5.00), and omeprazole (1.15, 1.38). Promethazine interacted with tegaserod (1.94, 4.64). In vitro investigation showed that these DDIs were unlikely to result from inhibition of drug metabolism by CYP450 enzymes or from inhibition of hepatic uptake via the membrane transporter OATP1B1/1B3. However, we did observe in vitro synergistic myotoxicity of simvastatin and desloratadine, suggesting a role in loratadine–simvastatin interaction. This interaction was epidemiologically confirmed (odds ratio 95% CI = [2.02, 3.65]) using the data from the US Food and Drug Administration Adverse Event Reporting System.</description><subject>Adverse Drug Reaction Reporting Systems</subject><subject>Animals</subject><subject>Biological Transport</subject><subject>Biotransformation</subject><subject>Cell Line</subject><subject>Cytochrome P-450 Enzyme Inhibitors - adverse effects</subject><subject>Cytochrome P-450 Enzyme Inhibitors - pharmacokinetics</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Interactions</subject><subject>Drug Synergism</subject><subject>Drug-Related Side Effects and Adverse Reactions - diagnosis</subject><subject>Drug-Related Side Effects and Adverse Reactions - epidemiology</subject><subject>Drug-Related Side Effects and Adverse Reactions - etiology</subject><subject>Drug-Related Side Effects and Adverse Reactions - metabolism</subject><subject>Humans</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - pathology</subject><subject>Muscular Diseases - chemically induced</subject><subject>Muscular Diseases - diagnosis</subject><subject>Muscular Diseases - epidemiology</subject><subject>Muscular Diseases - metabolism</subject><subject>Odds Ratio</subject><subject>Organic Anion Transporters - antagonists & inhibitors</subject><subject>Organic Anion Transporters - metabolism</subject><subject>Rats</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><subject>Translational Medical Research - methods</subject><subject>United States - epidemiology</subject><subject>United States Food and Drug Administration</subject><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kU1v0zAchy3ExLoN8Q2QbxxQNjt-SzggVWV0Heu2Q9GO1j-O0xiyJLKzQb497gLVOOziF_0eP5Z_RugdJaeUkPTM9MMpFeQVmlHB0kQKJl6jGSEkT_KUyUN0FMKPuOV5lr1Bh6nIlciomKFxVdp2cJUzMLiuxdCWeG1NDa0LgzN41T7auNhOaVfhL_5hm-yGGA3Wg9kFAc9D6IyDwZb4zg01Xo9dD0M9fsJzvPHQhubJAA2e973vwNQn6KCCJti3f-dj9P3r-WZxkVzdLFeL-VViOGck4VlBlK0gLzJlVSUlM6RgnMkipRlLpRGCU6NMVhTSKAqgqlyWucxFaZQsCDtGnydv_1Dc29LE53podO_dPfhRd-D0_0nrar3tHjWXkguRRcGHSWB8F4K31f4sJXrXvo7t69h-JN8_v2rP_as7Ah8n4Jdr7PiSRy9uN5Mumej4Ffb3ngb_U0vFlNB310t9zdjl8tuax8Ufd8OgPw</recordid><startdate>201509</startdate><enddate>201509</enddate><creator>Han, X</creator><creator>Quinney, SK</creator><creator>Wang, Z</creator><creator>Zhang, P</creator><creator>Duke, J</creator><creator>Desta, Z</creator><creator>Elmendorf, JS</creator><creator>Flockhart, DA</creator><creator>Li, L</creator><general>Blackwell Publishing Ltd</general><general>John Wiley and Sons Inc</general><scope>BSCLL</scope><scope>24P</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>5PM</scope></search><sort><creationdate>201509</creationdate><title>Identification and Mechanistic Investigation of Drug-Drug Interactions Associated With Myopathy: A Translational Approach</title><author>Han, X ; Quinney, SK ; Wang, Z ; Zhang, P ; Duke, J ; Desta, Z ; Elmendorf, JS ; Flockhart, DA ; Li, L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4430-48b07efa9b87e7f663c0b3436b218326c5541c7c8bb6c71aa7f96d9695dc76b03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adverse Drug Reaction Reporting Systems</topic><topic>Animals</topic><topic>Biological Transport</topic><topic>Biotransformation</topic><topic>Cell Line</topic><topic>Cytochrome P-450 Enzyme Inhibitors - adverse effects</topic><topic>Cytochrome P-450 Enzyme Inhibitors - pharmacokinetics</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Interactions</topic><topic>Drug Synergism</topic><topic>Drug-Related Side Effects and Adverse Reactions - diagnosis</topic><topic>Drug-Related Side Effects and Adverse Reactions - epidemiology</topic><topic>Drug-Related Side Effects and Adverse Reactions - etiology</topic><topic>Drug-Related Side Effects and Adverse Reactions - metabolism</topic><topic>Humans</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - pathology</topic><topic>Muscular Diseases - chemically induced</topic><topic>Muscular Diseases - diagnosis</topic><topic>Muscular Diseases - epidemiology</topic><topic>Muscular Diseases - metabolism</topic><topic>Odds Ratio</topic><topic>Organic Anion Transporters - antagonists & inhibitors</topic><topic>Organic Anion Transporters - metabolism</topic><topic>Rats</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><topic>Translational Medical Research - methods</topic><topic>United States - epidemiology</topic><topic>United States Food and Drug Administration</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Han, X</creatorcontrib><creatorcontrib>Quinney, SK</creatorcontrib><creatorcontrib>Wang, Z</creatorcontrib><creatorcontrib>Zhang, P</creatorcontrib><creatorcontrib>Duke, J</creatorcontrib><creatorcontrib>Desta, Z</creatorcontrib><creatorcontrib>Elmendorf, JS</creatorcontrib><creatorcontrib>Flockhart, DA</creatorcontrib><creatorcontrib>Li, L</creatorcontrib><collection>Istex</collection><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><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>Han, X</au><au>Quinney, SK</au><au>Wang, Z</au><au>Zhang, P</au><au>Duke, J</au><au>Desta, Z</au><au>Elmendorf, JS</au><au>Flockhart, DA</au><au>Li, L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification and Mechanistic Investigation of Drug-Drug Interactions Associated With Myopathy: A Translational Approach</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><addtitle>Clin. Pharmacol. Ther</addtitle><date>2015-09</date><risdate>2015</risdate><volume>98</volume><issue>3</issue><spage>321</spage><epage>327</epage><pages>321-327</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><abstract>Myopathy is a group of muscle diseases that can be induced or exacerbated by drug–drug interactions (DDIs). We sought to identify clinically important myopathic DDIs and elucidate their underlying mechanisms. Five DDIs were found to increase the risk of myopathy based on analysis of observational data from the Indiana Network of Patient Care. Loratadine interacted with simvastatin (relative risk 95% confidence interval [CI] = [1.39, 2.06]), alprazolam (1.50, 2.31), ropinirole (2.06, 5.00), and omeprazole (1.15, 1.38). Promethazine interacted with tegaserod (1.94, 4.64). In vitro investigation showed that these DDIs were unlikely to result from inhibition of drug metabolism by CYP450 enzymes or from inhibition of hepatic uptake via the membrane transporter OATP1B1/1B3. However, we did observe in vitro synergistic myotoxicity of simvastatin and desloratadine, suggesting a role in loratadine–simvastatin interaction. This interaction was epidemiologically confirmed (odds ratio 95% CI = [2.02, 3.65]) using the data from the US Food and Drug Administration Adverse Event Reporting System.</abstract><cop>United States</cop><pub>Blackwell Publishing Ltd</pub><pmid>25975815</pmid><doi>10.1002/cpt.150</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0009-9236 |
| ispartof | Clinical pharmacology and therapeutics, 2015-09, Vol.98 (3), p.321-327 |
| issn | 0009-9236 1532-6535 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4664558 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adverse Drug Reaction Reporting Systems Animals Biological Transport Biotransformation Cell Line Cytochrome P-450 Enzyme Inhibitors - adverse effects Cytochrome P-450 Enzyme Inhibitors - pharmacokinetics Dose-Response Relationship, Drug Drug Interactions Drug Synergism Drug-Related Side Effects and Adverse Reactions - diagnosis Drug-Related Side Effects and Adverse Reactions - epidemiology Drug-Related Side Effects and Adverse Reactions - etiology Drug-Related Side Effects and Adverse Reactions - metabolism Humans Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Muscular Diseases - chemically induced Muscular Diseases - diagnosis Muscular Diseases - epidemiology Muscular Diseases - metabolism Odds Ratio Organic Anion Transporters - antagonists & inhibitors Organic Anion Transporters - metabolism Rats Risk Assessment Risk Factors Translational Medical Research - methods United States - epidemiology United States Food and Drug Administration |
| title | Identification and Mechanistic Investigation of Drug-Drug Interactions Associated With Myopathy: A Translational Approach |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T16%3A16%3A19IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-istex_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Identification%20and%20Mechanistic%20Investigation%20of%20Drug-Drug%20Interactions%20Associated%20With%20Myopathy:%20A%20Translational%20Approach&rft.jtitle=Clinical%20pharmacology%20and%20therapeutics&rft.au=Han,%20X&rft.date=2015-09&rft.volume=98&rft.issue=3&rft.spage=321&rft.epage=327&rft.pages=321-327&rft.issn=0009-9236&rft.eissn=1532-6535&rft_id=info:doi/10.1002/cpt.150&rft_dat=%3Cistex_pubme%3Eark_67375_WNG_N33JGKM4_N%3C/istex_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/25975815&rfr_iscdi=true |